INTRODUCTION TO NEUROPHARMACOLOGY

Neuropharmacology is the scientific study of the effects of drugs on the nervous system. Its
primary focus is the actions of medications for psychiatric and neurologic disorders as well as
those of drugs of abuse. Neuropharmacology also uses drugs as tools to form a better
understanding of normal nervous system functioning. There are two main branches of
neuropharmacology: behavioral and molecular.

Behavioral neuropharmacology focuses on the study of how drugs affect human behavior
(neuropsychopharmacology), including the study of how drug dependence and addiction affect
the human brain.

Molecular neuropharmacology involves the study of neurons and

their neurochemical interactions, with the overall goal of developing drugs that have beneficial
effects on neurological function. Both of these fields are closely connected, since both are
concerned with the interactions

The goal of neuropharmacology is to apply information about drugs and their mechanisms of
action to develop safer, more effective treatments and eventually curative and preventive
measures for a host of nervous system abnormalities. The importance of neuropharmacology to
medical practice, and to society at large, is difficult to overstate. Drugs that act on the nervous
system, including antidepressant, antianxiety, anticonvulsant, and antipsychotic agents, are
among the most widely prescribed medications.

NEUROTRANSMITTERS AND RECEPTOR SYSTEM IN BRAIN

SEROTININ
Serotonin was first recognized as a powerful vasoconstrictor in blood serum. It was isolated
in 1948 by Page and was later found to be associated with the central nervous system.

The chemical name for serotonin is 5-hydoxytryptamine which is

often abbreviated to 5-HT.

Serotonin is naturally produced in the Pineal gland which lies deep at

the centre of the human brain. The average adult human possesses
only 5 to 10 mg of serotonin, 90 % of which is in the intestine and the
rest in blood platelets and the brain.

One role of this 'wonder drug' is as a neurotransmitter, allowing numerous functions in the
human body including the control of appetite, sleep, memory and learning, temperature

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 regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine
regulation and depression.

5-HT Receptors:
• 5-HT1A Receptors

• 5-HT1B Receptors

• 5-HT1D Receptors

• 5-ht1E Receptors

• 5-HT1F Receptors

5-HT1A Receptors
The serotonin 5-HT1A receptor was the first 5-HT receptor to be fully sequenced. 5-
HT1A receptor binding sites are located primarily in limbic brain areas, notably the
hypothalamus and cortical areas. The human gene encoding this receptor has been localized to
chromosome 5.
5-HT1B Receptors
Serotonin 5-HT1B receptors, previously known as 5-HT1D receptors, are primarily located in
the basal ganglia, striatum, hippocampus and vascular smooth muscle. 5-HT1B receptors play a
role in thermoregulation, respiration, appetite control, sexual behavior and aggression.
5-HT1D Receptors
Serotonin 5-HT1D receptors, previously known as 5-HT1Dα receptors, are located primarily in
the basal ganglia, hippocampus, cortex, spinal cord and vascular smooth muscle cells. 5-
HT1D receptors are thought to be involved in neuropsychiatric disorders such as depression.
5-ht1E Receptors
Serotonin 5-ht1E receptors are primarily located in the frontal cortex, caudate putamen,
claustrum, hippocampus, and amygdala. The human 5-ht1E receptor gene has been localized to
chromosome 6 (6q14-q15); the receptor is closely related to the serotonin 5-HT1Freceptor
5-HT1F Receptors
Serotonin 5-HT1F receptors, previously known as 5-HT1Eβ receptors, are located primarily in
the hippocampus, cortex and dorsal raphe nucleus. The human 5-HT1F receptor is closely related
to the 5-ht1E receptor and its gene has been localized to chromosome 3

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 NON-ADRENLINE

Norepinephrine, also called noradrenaline, substance that is released predominantly from

the ends of sympathetic nerve fibres and that acts to increase the force of skeletal
muscle contraction and the rate and force of contraction of the heart. The actions of
norepinephrine are vital to the fight-or-flight response, whereby the body prepares to react to
or retreat from an acute threat.
Norepinephrine is classified structurally as a catecholamine—it contains a catechol group (a
benzene ring with two hydroxyl groups) bound to an amine (nitrogen-containing) group
Receptors :
l-Norepinephrine is a naturally occurring catecholamine hormone that functions as a
neurotransmitter in the sympathetic nervous system. Norepinephrine directly stimulates
adrenergic receptors. Stimulation of alpha-adrenergic receptors causes vasoconstriction of the
radial smooth muscle of the iris, arteries, arterioles, veins, urinary bladder, and the sphincter
of the gastrointestinal tract. Stimulation of beta-1 adrenergic receptors causes an increase in
myocardial contractility, heart rate, automaticity, and atrioventricular (AV) conduction while
stimulation of beta-2 adrenergic receptors causes bronchiolar and vascular smooth muscle
dilatation.

 ACETYLCHOLINE
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types
of animals, including humans, as a neurotransmitter—a chemical message released by nerve cells
to send signals to other cells [neurons, muscle cells, and gland cells]. Its name is derived from its
chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are
affected by acetylcholine are referred to as cholinergic. Substances that interfere with
acetylcholine activity are called anticholinergics. Acetylcholine is the neurotransmitter used at
the neuromuscular junction—in other words, it is the chemical that motor neurons of the nervous
system release in order to activate muscles. Acetylcholine is also a neurotransmitter in
the autonomic nervous system, both as an internal transmitter for the sympathetic nervous
system and as the final product released by the parasympathetic nervous system.
Receptors:
There are two types of acetylcholine receptors (AChR) that bind acetylcholine and transmit its
signal: muscarinic AChRs and nicotinic AChRs, which are named after the agonists muscarine
and nicotine, respectively. These receptors are functionally different, the muscarinic type being
G-protein coupled receptors (GPCRs) that mediate a slow metabolic response via second
messenger cascades, while the nicotinic type are ligand-gated ion channels that mediate a fast
synaptic transmission of the neurotransmitter.

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Muscarinic Cholinergic Receptors:
Muscarinic receptors are characterised through their interaction with muscarine, a water-soluble
toxin derived from the mushroom. The muscarinic AChRs occur primarily in the CNS, and are
part of a large family of G-protein-coupled receptors (‘G proteins’), which use an intracellular
secondary messenger system involving an increase of intracellular calcium to transmit signals
inside cells. Binding of acetylcholine to a muscarinic AChR causes a conformational change in
the receptor. Muscarinic receptors are involved in a large number of physiological functions
including heart rate and force, contraction of smooth muscles and the release of
neurotransmitters.

Nicotinic cholinergic receptors

Nicotinic receptors are characterised through their interaction with nicotine in tobacco. The
nicotinic AChRs are ligand-gated ion channels that form pores in cells’ plasma membranes,
mediating fast signal transmission at synapses. Nicotinic AChRs are involved in a wide range of
physiological processes, and can be either neuronal or muscle-type. Muscle-type nicotinic
AChRs are localised at neuromuscular junctions, where an electrical impulse from a neuron to a
muscle cell signals contraction and is responsible for muscle tone; as such, these receptors are
targets for muscle relaxants. The many types of neuronal nicotinic AChRs are located at
synapses between neurons, such as in the CNS where they are involved in cognitive function,
learning and memory, arousal, reward, motor control and analgesia.
The binding of acetylcholine to nicotinic AChRs brings about their activation. When two
molecules of acetylcholine bind a nicotinic AchR, a conformational change occurs in the
receptor, resulting in the formation of an ion pore. At the neuromuscular junction, the opening
of a pore produces a rapid increase in the cellular permeability of sodium and calcium ions,
resulting in the depolarisation and excitation of the muscle cell, thereby producing a muscular
contraction.

DOPAMINE:
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is an organic chemical of
the catecholamine and phenethylaminefamilies. It functions both as a hormone and a
neurotransmitter, and plays several important roles in the brain and body. It is
an aminesynthesized by removing a carboxyl group from a molecule of its precursor
chemical L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized
in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical
released by neurons (nerve cells) to send signals to other nerve cells. The brain includes several
distinct dopamine pathways, one of which plays a major role in the motivational component
of reward-motivated behavior. The anticipation of most types of rewards increases the level of
dopamine in the brain,[2] and many addictive drugs increase dopamine release or block its
reuptake into neurons following release. Other brain dopamine pathways are involved in motor
control and in controlling the release of various hormones. These pathways and cell
groups form a dopamine system which is neuromodulatory.
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Receptors:
There are five subtypes of dopamine receptors, D1, D2, D3, D4, and D5, which are
members of the large G-protein coupled receptor super family. The dopamine receptor
subtypes are divided into two major subclasses: types 1 and 5 are similar in structure and
drug sensitivity, and these two receptors are referred to as the "D1like" group or class of
receptors. Dopamine receptor types 2, 3, and 4 are called the "D2like" group. Dopamine
plays central role in pleasurable reward behavior, inhibition of prolactin production
(involved in lactation), sleep, mood, attention, learning, behavior, control of nausea and
vomiting and pain processing. In addition it also involved in controlling movement,
emotion and cognition.

Due to extensive localization of dopamine receptor to brain areas and its role in wide
range of functions, dopaminergic dysfunction has been implicated in the pathophysiology
of schizophrenia, mood disorders, obsessive compulsive disorder (OCD), autism
spectrum disorders, attention deficit–hyperactivity disorder (ADHD), tourette's
syndrome, substance dependency, Parkinson's disease and other disorders.

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 BRAIN DISORDERS AND DRUGS USED TO TREAT THEM
When your brain is damaged, it can affect many different things, including your memory, your
sensation, and even your personality. Brain disorders include any conditions or disabilities that
affect your brain. This includes conditions that are caused by:
 illness
 genetics
 traumatic injury

PARKINSON’S DISEASE
Parkinson's disease is a neurodegenerative disease described by the selective loss of
dopaminergic neurons located in the substantianigra. Today, the most commonly used drug
to combat this disease is levodopa or L-DOPA. This precursor to dopamine can penetrate
through the blood–brain barrier, whereas the neurotransmitter dopamine cannot.
Parkinson's signs and symptoms may include:
 Tremor. A tremor, or shaking, usually begins in a limb, often your hand or fingers. You
may a rub your thumb and forefinger back-and-forth, known as a pill-rolling tremor. Your
hand may tremor when it's at rest.
 Slowed movement (bradykinesia). Over time, Parkinson's disease may slow your
movement, making simple tasks difficult and time-consuming. Your steps may become
shorter when you walk. It may be difficult to get out of a chair. You may drag your feet as
you try to walk.
 Rigid muscles. Muscle stiffness may occur in any part of your body. The stiff muscles can
be painful and limit your range of motion.
 Impaired posture and balance. Your posture may become stooped, or you may have
balance problems as a result of Parkinson's disease.
DRUGS USED FOR PARKINSON’S DISEASE
 COMT (catechol-O-methyl transferase) inhibitors
 Levodopa
 Dopamine agonists

 ALZHEIMER’S DISEASE

Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate)
and die. Alzheimer's disease is the most common cause of dementia — a continuous decline in
thinking, behavioral and social skills that disrupts a person's ability to function independently.
The early signs of the disease may be forgetting recent events or conversations. As the disease
progresses, a person with Alzheimer's disease will develop severe memory impairment and lose
the ability to carry out everyday tasks. Current Alzheimer's disease medications may temporarily
improve symptoms or slow the rate of decline.

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DRUGS FOR ALZHEIMER’S DISEASE:

MULTIPLE SCLEROSIS:
Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central
nervous system).In MS, the immune system attacks the protective sheath (myelin) that covers
nerve fibers and causes communication problems between your brain and the rest of your body.
Eventually, the disease can cause permanent damage or deterioration of the nerves.
The cause of multiple sclerosis is unknown. It's considered an autoimmune disease in which the
body's immune system attacks its own tissues. In the case of MS, this immune system
malfunction destroys the fatty substance that coats and protects nerve fibers in the brain and
spinal cord (myelin).

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Oral treatment includes

 Fingolimod (Gilenya). This once-daily oral medication reduces relapse rate.

 Dimethyl fumarate (Tecfidera). This twice-daily oral medication can reduce
relapses

Infusion treatments include:

 Ocrelizumab (Ocrevus). This humanized immunoglobulin antibody medication is the

only DMT approved by the FDA to treat both the relapse-remitting and primary-
progressive forms of MS

 Mitoxantrone. This immunosuppressant drug can be harmful to the heart and is

associated with development of blood cancers. As a result, its use in treating MS is
extremely limited. Mitoxantrone is only rarely used to treat severe, advanced MS.

ANXIOLYTIC AND SEDATIVE DRUGS

Anxiety is an unpleasant state of tension, apprehension, or uneasiness a fear that seems to arise
from a sometimes unknown source. Disorders involving anxiety are the most common mental
disturbances. The physical symptoms of severe anxiety are similar to those of fear (such as
tachycardia, sweating, trembling, and palpitations) and involve sympathetic activation. Episodes
of mild anxiety are common life experiences and do not warrant treatment. However, the
symptoms of severe, chronic, debilitating anxiety may be treated with antianxiety drugs
(sometimes called anxiolytic or minor tranquilizers) and/or some form of behavioral or
psychotherapy. Because many of the antianxiety drugs also cause some sedation, the same drugs
often function clinically as both anxiolytic and hypnotic (sleep-inducing) agents. In addition,
some have anticonvulsant activity. Figure 9.1 summarizes the anxiolytic and hypnotic agents.
Though also indicated for certain anxiety disorders, the selective serotonin reuptake inhibitors
(SSRIs) will be presented in the chapter discussing antidepressants.

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 A. BENZODIAZAPENES

Benzodiazepines are the most widely used anxiolytic drugs. They have largely replaced
barbiturates and meprobamate in the treatment of anxiety, because the benzodiazepines are safer
and more

Mechanism of action

Benzodiazepines work in the central nervous system, selectively occupying certain protein areas
in the brain called GABA-A receptors. There are three types of GABA (gamma-aminobutyric)
receptors in the brain: GABA-A, GABA-B, and GABA-C. GABA is the main inhibitory
neurotransmitter in the brain (a chemical that help to block a nerve action). GABA helps to
regulate movement control, sight, anxiety, and many other brain functions.

Benzodiazepines enhance responses to the inhibitory neurotransmitter GABA by opening

GABA-activated chloride channels and allowing chloride ions to enter the neuron. This action
allows the neuron to become negatively charged and resistant to excitation, which leads to the
various anti-anxiety, sedative, or anti-seizure activity seen with these drugs.

Drugs:
 alprazolam (Xanax, Xanax XR)
 clobazam (Onfi)
 clonazepam (Klonopin)
 clorazepate (Tranxene)
 chlordiazepoxide (Librium)
 diazepam (Valium, Diastat Acudial, Diastat)
 estazolam (Prosom is a discontinued brand in the US)

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  lorazepam (Ativan)
 oxazepam (Serax is a discontinued brand in the US)
 temazepam (Restoril)
 triazolam (Halcion)

Pharmacokinetics

1) Absorption and distribution:

The benzodiazepines are lipophilic, and they are rapidly and completely absorbed after oral
administration and distribute throughout the body.

2) Duration of actions:

The half-lives of the benzodiazepines are very important clinically, because the duration of
action may determine the therapeutic usefulness. The benzodiazepines can be roughly
divided into short-, intermediate-, and long-acting groups .

Adverse effects:
The side effects of benzodiazepine usage may include:
 drowsiness
 confusion
 dizziness
 trembling
 impaired coordination
 vision problems
 grogginess
 feelings of depression
 headache

Indications:
 anterograde amnesia prior to a medical procedure (e.g. surgery). Definition: you cannot
remember events experienced while under the influence of the drug. This contrasts
with retrograde amnesia where memories created “before” the event are lost.
 anxiety disorders (e.g. generalized anxiety disorder, anxiety associated with depressive
symptoms)(e.g. alprazolam, lorazepam)
 insomnia (e.g. flurazepam, temazepam)

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  muscle relaxant (e.g. diazepam - at doses that cause little sedation)
 panic disorders (alprazolam, clonazepam)
 preoperative apprehension & anxiety
 seizure disorders - absence seizures, akinetic seizures (e.g. clonazepam)
 status epilpeticus (e.g. lorazepam)
 withdrawal symptoms of acute alcoholism (e.g. chlordiazepoxide, diazepam)

B. BARBITURATES

The barbiturates were formerly the mainstay of treatment to sedate the patient or to induce and
maintain sleep. Today, they have been largely replaced by the benzodiazepines, primarily
because barbiturates induce tolerance,
drug-metabolizing enzymes, physical dependence, and are associated with very severe
withdrawal symptoms. Foremost is their ability to cause coma in toxic doses. Certain
barbiturates, such as the very short-acting thiopental, are still used to induce anesthesia

Mechanism of action

The sedative-hypnotic action of the barbiturates is due to their interaction with GABAA
receptors, which enhances GABAergic transmission. The binding site is distinct from that of the
benzodiazepines. Barbiturates potentiate GABA action on chloride entry into the neuron by
prolonging the duration of the chloride channel openings. In addition, barbiturates can block
excitatory glutamate receptors. Anesthetic concentrations of pentobarbital also block high-
frequency sodium channels. All of these molecular actions lead to decreased neuronal activity.
.

Pharmacokinetics

Barbiturates are absorbed orally and distributed widely throughout the body. All barbiturates
redistribute in the body from the brain to the splanchnic areas, to skeletal muscle, and finally, to
adipose tissue. This movement is important in causing the short duration of action of thiopental
and similar short-acting derivatives. They readily cross the placenta and can depress the fetus.
Barbiturates are metabolized in the liver, and inactive metabolites are excreted in the urine.

List of drugs
Examples of barbiturates availablE are

 amobarbital
 butabarbital
 pentobarbital secobarbital

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  belladonna and phenobarbital
 butalbital/acetaminophen/caffeine
 butalbital/aspirin/caffeine

Side Effects:

Common side offects of Barbiturates are:

 Insomnia.
 An increased sensitivity to sound.
 An increased sensitivity to pain.
 Increased perspiration.
 Irritability.
 Hallucinations or psychosis (rare).
 Paranoia.
 Memory and attention impairments.
 Emotional instability.
 Suicidal ideation.

Indications:
 sedative for short term treatment of insomnia (barbiturates lose effectiveness after ~2
weeks)
 preanesthetic
 long term management of simple partial seizures, tonic-clonic seizures
 an alternative drug for the emergency treatment of status epilepticus;
lorazepam/diazepam, phenytoin/fosphenytoin & valproate are typical drugs of choice before
barbiturates.

ANTI- DEPRESSANTS
Antidepressants are medications that can help relieve symptoms of depression, social anxiety
disorder, anxiety disorders, seasonal affective disorder, and dysthymia, or mild chronic
depression, as well as other conditions.
They aim to correct chemical imbalances of neurotransmitters in the brain that are believed to be
responsible for changes in mood and behavior.

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 Selective Serotonin Reuptake Inhibitors:
Mechanism of action:

The selective serotonin reuptake inhibitors (SSRIs) are a group of chemically diverse
antidepressant drugs that specifically inhibit serotonin reuptake, having 300- to 3000-fold greater
selectivity for the serotonin transporter as compared to the norepinephrine transporter. This
contrasts with the tricyclic antidepressants (see p. 145) that nonselectively inhibit the uptake of
norepinephrine and serotonin (Figure 12.3). Both of these antidepressant drug classes exhibit
little ability to block the dopamine transporter. Moreover, the SSRIs have little blocking activity
at muscarinic, α-adrenergic, and histaminic H1 receptors. Therefore, common side effects
associated with tricyclic antidepressants, such as orthostatic hypotension, sedation, dry mouth,
and blurred vision, are not commonly seen with the SSRIs. Because they have fewer adverse
effects and are relatively safe even in overdose, the SSRIs have largely replaced tricyclic
antidepressants and monoamine oxidase inhibitors as the drugs of choice in treating depression.

PHARMACOKINETICS:

All of the SSRIs are well absorbed after oral administration. Peak levels are seen in
approximately 2 to 8 hours.

ADVERSE EFFECTS :

Although the SSRIs are considered to have fewer and less severe adverse effects than the
tricyclic antidepressants and monoamine oxidase inhibitors, the SSRIs are not without
troublesome adverse effects, such as, headache, sweating, anxiety and agitation, gastrointestinal
effects (nausea, vomiting, diarrhea), weakness and fatigue, sexual dysfunction, changes in
weight, sleep disturbances (insomnia and somnolence), and the above-mentioned potential for
drug-drug interactions

DRUGS
The common drugs are:
 Citalopram
 Escitalopram
 Fluoxetine
 Fluvoxamine
 Paroxetine
 Sertraline

Indications

 Depression - all SSRIs are licensed for this indication; paroxetine is licensed only for the
treatment of major depression.
 Panic disorder - citalopram, escitalopram, paroxetine, sertraline.
 Social anxiety disorder/social phobia - escitalopram, paroxetine.
 Bulimia nervosa - fluoxetine.

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 Obsessive-compulsive disorder - fluoxetine, escitalopram, fluvoxamine, paroxetine, sertraline
(the latter under specialist supervision in children) .
 Post-traumatic stress disorder - paroxetine, sertraline (the latter in females only).
 Generalised anxiety disorder - paroxetine, escitalopram.
 Premenstrual syndrome (unlicensed)

ANTILEPTICS
Epilepsy is a central nervous system (neurological) disorder in which brain activity becomes
abnormal, causing seizures or periods of unusual behavior, sensations, and sometimes loss of
awareness.Antiepileptics are used for the prevention of seizures and associated complications.
They are also indicated for acute treatment of seizures including status epilepticus and febrile
seizures.
Seizure symptoms can vary widely. Some people with epilepsy simply stare blankly for a few
seconds during a seizure, while others repeatedly twitch their arms or legs. Having a single
seizure doesn't mean you have epilepsy. At least two unprovoked seizures are generally required
for an epilepsy diagnosis.

Drugs for epilepsy:

First line Second line

Partial Carbamazepine Gabapentin, lamotrigine, ,
phenytoin, , valproate
Generalised tonic-clonic Valproate, carbamazepine Lamotrigine, oxcarbazepine,
phenytoin, topiramate
Absence Valproate, ethosuximide Clobazam, clonazepam,
lamotrigine
Myoclonic Valproate Clobazam, clonazepam,
phenobarbitone

Mechanism of action

Antiepileptics have various mechanisms of actions to try and prevent rapid, repetitive,
stimulation of the brain that causes seizure activity. Topamax (Topiramate), Tegretol
(Carbamazepine), Epilim (Valproate) and Lamical (Lamotrigine) and work by blocking voltage
gated sodium channels and hence prevent the repeated stimulation. Neurontin (Gabapentin) and
Gabitril (Tiagabine) elevates GABA levels, a chemical messenger that stops repeated
stimulation. Some if this activity is also demonstrated by Topamax (Topiramate). Lyrica
(Pregabalin) is newer drug which is an analogue GABA with analgesic, anxiolytic and
anticonvulsant activity.

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Adverse Effects:
The side effects for each type of medication vary but the most common side effects that occur in
less than 10% of patients are:

 Drowsiness
 Ataxia
 Dizziness
 Blurred vision
 Headache
 Nausea
 Vomiting
 Diarrhoea
 Constipation

PHARMACOKINETICS:
All of the AEDs are well absorbed after oral administration. Peak levels are seen in
approximately 4 to 12 hours.

Indications:
 Drugs are indicated for:
 epilepsy
 trigeminal neuralgia
 absence (petit mal) seizures 5
 complex partial seizures; tonic-clonic (grand mal) seizures
 postherpetic neuralgia

ANTI-PSYCHOTICS
Antipsychotics are a group of drugs that are used to treat serious mental health conditions such
as psychosis as well as other emotional and mental conditions. In addition, they are prescribed
for the treatment of intractable hiccoughs and pain that can result from restlessness. Anti-
psychotics are classified into 2 classes that are first generation and second generation anti-
psychotics.

Mechanism of action :
Antipsychotics change the levels of chemicals in your brain called neurotransmitters — the
chemicals that carry messages around your brain. The neurotransmitter most targeted by
antipsychotics is called dopamine.Changing the levels of these chemicals reduces, in almost all
cases, the hallucinations and delusions of psychosis. In some cases, they also improve your mood
and reduce anxiety.

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Adverse Effects:
Common side effects of antipsychotic medications include:

 Blurred vision
 Dry mouth
 Drowsiness
 Muscle spasms or tremors
 Weight gain

Pharmacokinetics:
Most of the antipsychotics are very lipophilic and cross lipoidal membranes freely. When
administered orally, they are well absorbed and undergo substantial pre-systemic elimination
(bioavailability: 10-70%), are highly bound to plasma proteins (75-99%) and tissues, and are
extensively distributed. Primary route of elimination for most of antipsychotics is hepatic

DRUGS:
FIRST GENERATION ANTI-PSYCHOTICS: SECOND GENERATION ANTI-
Typical – antipsychotics are divided into two groups: PSYCHOTICS:
 High potency:  Aripiprazole
 Chlorpromazine  Clozapine
 Lurosidone
 Prochlorperazine
 Olanzapine
 Thioridazine
 Resperidone
 Ziprasidone
 Low potency:
 Fluphenazine
 Haloperidol
 Thiothixene
 Pimozide

CNS STIMULANTS

Two groups of drugs that act primarily to stimulate the central nervous system (CNS). The first
group, the psychomotor stimulants, cause excitement and euphoria, decrease feelings of fatigue,
and increase motor activity. The second group, the hallucinogens, or psychotomimetic drugs,
produce profound changes in thought patterns and mood, with little effect on the brainstem and
spinal cord.

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Mechanism Of Action:
Stimulants can have a wide variety of mechanisms. Many stimulants exert their effects through
manipulations of monoamine neurotransmission. Monoamines are a class of neurotransmitter
relevant in reward, motivation, temperature regulation and pain sensation that
include dopamine, norepinephrine, and serotonin. Stimulants usually block the reuptake or
stimulate the efflux of dopamine and norepinephrine resulting in increased activity of their
circuits. Some stimulants, notably those with empathogenic and hallucinogeniceffects alter
serotonergic neurotransmission. Interference with vesicular storage, activating TAAR1, and
reversing the flow of monoamine transporters may play a mechanism in the activity of these
drugs. Adrenergic stimulants, such as ephedrine, may act by directly binding and activating the
receptors that norepinephrine and epinephrine normally bind to (adrenergic receptors), producing
sympathomimetic effects. Some drugs, such as MDMA and derivatives may decrease regulatory
capability by antagonizing regulatory pre-synaptic auto receptors.[43] Caffeine is a notable
exception, as it exerts its effects by antagonizing adenosine receptors instead of acting directly
on monoamines

Drugs:
 Methylxantine
 Nicotine
 Cocaine
 Amphetamine
 Methylphenidate
 Varenicline

Adverse Effects:
 Depersonalization (a feeling that you are an observer of yourself)
 Dizziness.
 Facial tics.
 Headaches.
 Inability to sleep.
 Increased blood pressure.
 Increased rate of breathing.
 Irritability.
Pharmacokinetics:
 large vol. of distribution quickly metabolized: half-life 30-90 minutes
 principal metabolites: a) Ecogonine methylester - inactive b) Benzoylecogonine - inactive
c)nor cocaine
 active half lives of metabolites: 4 to 6 hrs. metabolites
 Excreted in urine Drug Testing: BE - detectable for 1-3 days
 Cocaine - detectable for a few hours

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Indication:

CNS stimulants may be useful for the treatment of certain conditions characterized by symptoms
such as prolonged fatigue, inability to concentrate, or excessive sleepiness. CNS stimulants may
also be used to help with weight loss in people who are morbidly obese. CNS stimulants have
been used for the following conditions:

 Attention deficit disorder

 Chronic lethargy
 Morbid obesity unresponsive to other treatments
 Narcolepsy
 Neonatal apnea
 Postural orthostatic tachycardia syndrome
 Prolonged depression that is unresponsive to traditional antidepressants

Unfortunately, some people misuse CNS stimulants for their ability to increase energy levels.
Some CNS stimulants also create a brief feeling of euphoria or temporarily increase self-
confidence.

OPOIDS

Opioids interactstereospecifically with protein receptors on the membranes of certain cells in the
CNS, on nerve terminals in the periphery, and on cells of the gastrointestinal tract and other
anatomic regions. The major effects of the opioids are mediated by three major receptor families.
These are designated by the Greek letters µ (mu), κ (kappa), and δ (delta). Each receptor
family exhibits a different specificity for the drug(s) it binds. The analgesic properties of the
opioids are primarily mediated by the µ receptors; however, the κ receptors in the dorsal horn
also contribute. For example, butorphanol and nalbuphine primarily owe their analgesic effect.

STRONG AGONIST:

Morphine
 Mechanism of action:
Opioids exert their major effects by interacting with opioid receptors in the CNS and in other
anatomic structures, such as the gastrointestinal tract and the urinary bladder. Opioids cause
hyperpolarization of nerve cells, inhibition of nerve firing, and presynaptic inhibition of
transmitter release. Morphine acts at κ receptors in Lamina I and II of the dorsal horn of the
spinal cord, and it decreases the release of substance P.

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  Pharmacokinetics:
Absorption of morphine from the gastrointestinal tract is slow and erratic. Significant first-pass
metabolism of morphine occurs in the liver; therefore, intramuscular, subcutaneous, or IV
injections produce the most reliable responses. Morphine rapidly enters all body tissues,
including the fetuses of pregnant women, and should not be used for analgesia during labor.
Infants born of addicted mothers show physical dependence on opiates and exhibit withdrawal
symptoms if opioids are not administered.

 Adverse effects:
Severe respiratory depression occurs and can result in death from acute opioid poisoning. A
serious effect of the drug is stoppage of respiratory exchange in patients with emphysema or
corpulmonale. Other effects include vomiting, dysphoria, and allergy-enhanced hypotensive
effects.
 Mechanism of action:
The actions of methadone are mediated by the µ receptors.

 Pharmacokinetics:
Methadone is readily absorbed following oral administration. It accumulates in tissues, where it
remains bound to protein, from which it is slowly released. The drug is biotransformed in the
liver and is excreted in the urine, mainly as inactive metabolites.

 Adverse effects:
Methadone can produce physical dependence like that of morphine.

MODERATE AGONISTS:
Codeine:
The analgesic actions of codeine [KOE-deen] are due to its conversion to morphine, whereas the
drug's antitussive effects are due to codeine itself. Thus, codeine is a much less potent analgesic
than morphine, but it has a higher oral effectiveness. Codeine shows good antitussive activity at
doses that do not cause analgesia. Codeine produces less euphoria than morphine. Codeine is
often used in combination with aspirin or acetaminophen

Propoxyphene:
The dextro isomer is used as an analgesic to relieve mild to moderate pain. The levo isomer is
not analgesic, but it has antitussive action. Propoxyphene is a weaker analgesic than codeine,
requiring approximately twice the dose to achieve an effect equivalent to that of codeine.
Propoxyphene is often used in combination with acetaminophen for an analgesia greater than
that obtained with either drug alone.

MIXED AGONISTS AND PARTIAL AGONISTS:

Drugs that stimulate one receptor but block another are termed mixed agonist-antagonists. The
effects of these drugs depend on previous exposure to opioids. In individuals who have not
recently received opioidS, mixed agonist-antagonists show agonist activity and are used to
relieve pain. In the patient with opioid dependence, the agonist-antagonist drugs may show
primarily blocking effects that is, produce withdrawal symptoms.

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Drugs;
 Pentazocine
 Buprenorphine
 Nalbuphine and butorphanol

OTHER ANALGESICS:
Tramadol:
Tramadol is a centrally acting analgesic that binds to the µ-opioid receptor. In addition, it
weakly inhibits reuptake of norepinephrine and serotonin. It is used to manage moderate to
moderately severe pain. Its respiratory-depressant activity is less than that of morphine.
Naloxone can only partially reverse the analgesia produced by tramadol or its active metabolite.
The drug undergoes extensive metabolism, and one metabolite is active.

Naloxone
Naloxone is used to reverse the coma and respiratory depression of opioid overdose.

Naltrexone
Naltrexone has actions similar to those of naloxone. It has a longer duration of action than
naloxone, and a single oral dose of naltrexone blocks the effect of injected heroin for up to 48
hours.

Nalmefene
Nalmefene is a parenteral opioid antagonist with actions similar to that of naloxone and
naltrexone. It can be administered IV, intramuscularly, or subcutaneously. Its half-life of 8 to10
hours

THERAPEUTIC GASES

Oxygen:

 Indication:
Oxygen therapy (delivery of oxygen at a higher concentration than room air (at a higher FiO2)) is
used to treat hypoxia, which is a condition of very low concentration of oxygen in the tissue.
Hypoxia is caused by hypoxemia a condition of low oxygen in the blood. This makes sense
because if there isn't enough oxygen in the blood, the blood can't deliver enough oxygen to the
body tissues as it circulates.

 Mechanism of action:
Oxygen can be delivered via variable intake devices (nasal prongs, Hudson masks), or in fixed
amounts via venturi masks or endotracheal tubes. Mechanism of action → The main action of
oxygen in the body is to participate in oxidative phosphorylation, which produces the ATP
required for cellular function.

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  Pharmacokinetics
Oxygen rapidly covert carboxyhemoglobin to oxyhemoglobin to avoid CO2 poisoning, it
dissolves in plasma thereby causing relief hypoxia to tissue.

 Side effects:
I. Dry mouth
II. Nosebleeds (epistaxis)
III. Runny nose (rhinorrhea)
IV. Sore nose
V. Dry nasal passages
VI. Burning sensation

Carbondioxide:

 Indication:
This is used to treat a condition called hypoplastic left heart syndrome, a heart defect where
completely saturated blood causes pressure, preventing it from passing from the left atrium to the
left ventricle of the heart.


Mechanism of action:
Though it is not metabolised in any conventional sense, CO2 undergoes chemical changes in the
bloodstream. Specifically, its transport in the blood resembles metabolism, in the sense that the
natural hydration reaction (which converts CO2 into H2CO3) is vigorously catalysed by carbonic
anhydrase in the red blood cells, with H+ and HCO3- the end products. This "metabolic process"
is discussed in greater detail in the chapters on the physiology of CO2 transport and the buffering
of acute respiratory acid-base disorders.

 Side effects
Carboxytherapy is a relatively safe procedure with almost no side effects. People may have
bruising at the injection site, specifically in the arms and legs. This bruising should clear up
within a week. People who get the procedure for fat reduction or cellulite also shouldn’t immerse
themselves in water for 24 hours, including swimming or using a bathtub.

Nitric Oxide:

 Indication:
Inhaled NO Is used in the management of infants with persistent PH and the role of exhaled NO
as a marker of disease activity in asthma and other chronic lung diseases

 Mechanism of action :
NO activates soluble guanylylcyclase (sGC) to produce cyclic guanosine monophosphate
(cGMP), which then activates cGMP dependent protein kinase (PKG) which results in the
activation of several regulatory mechanisms that decrease intracellular calcium and decrease

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vascular smooth muscle tone (ie, vasodilation) in precapillary resistance arterioles. Additional
effects of NO include suppression of both smooth muscle proliferation and platelet aggregation.

These properties have led to the development of inhaled NO and other agents that enhance the
NO/cGMP signaling pathway such as sildenafil and tadalafil (phosphodiesterase type-5 [PDE5]
inhibitors), or riociguat, ansGC stimulator. Inhaled NO has been shown to be effective at
reducing pulmonary vascular resistance at doses as low as 1 part per million (ppm). A
vasodilator effect of NO has been demonstrated with as little as 0.1 ppm and there appears to be
a threshold for pulmonary vasodilation that occurs at a dose of approximately 10 ppm.

 Pharmacokinetics:
NOS catalyzes a multi-step reaction in which L-arginine and oxygen are converted to L-citrulline
and NO. NO that is synthesized by vascular endothelial cells diffuses into adjacent vascular
smooth muscle and decreases vascular tone in the systemic and pulmonary circulation. When
administered by inhalation, it selectively dilates pulmonary vasculature in ventilated areas of the
lung. The vasodilating effect of inhaled NO has a rapid onset of action and a short half-life that
results in essentially no effect on systemic vessels making it a highly selective, short acting
pulmonary vasodilator and an ideal agent for pulmonary vasoreactivity testing.

 Side effects:
Nitric oxide causes few side effects, but your baby may have noisy breathing, blood in the urine,
or possibly a collapsed lung. There is also a possibility that the baby will have breathing
difficulties after the nitric oxide treatment is stopped.

Helium:

 Indication:
When a heliox gas mixture (79% helium and 21% oxygen) is produced, it has a viscosity similar
to, but a density nearly six times lowers than atmospheric air. Due to these properties, heliox has
potential applications in respiratory medicine.

 Mechanism of action:
Due to its lower density, inhalation of heliox results in significantly lower turbulence,
particularly in the more distal portions of the lung. This effect translates to a greater proportion
of laminar flow and lower overall airway resistance. The decreased turbulence effect results in
increased flow rates by up to 50% during heliox inhalation. This decreased turbulence remained
evident even when airflow was restricted, as in the case of obstructive lung disease.

 Side effects:
It can cause dizziness and even asphyxiation. Additional side effects include nausea, vomiting,
and/or loss of consciousness. Children may suffer lung damage as a result of inhaling it. Even

22
 frostbite may occur when it is inhaled directly from the tank. With each inhalation of helium,
oxygen is displaced or removed in favor of the helium. As a result, this causes a severe reduction
in the body’s general oxygen levels.

ANTIPARKINSON’S DRUGS AND NEURODEGENERATIVE DRUGS

ANTI PARKINSON’S DRUGS:

DRUG NAMES
Benztropine is indicated to be used as an adjunct in the therapy of all forms
of parkinsonism. It can also be used for the control of extrapyramidal disorders
due to neuroleptic drugs.
Benzatropine Drowsiness, dizziness, constipation, flushing, nervousness, blurred vision, or dry mouth may occur.
Benztropine belongs to a class of medication called anticholinergics that work by blocking a certain
natural substance (acetylcholine).

Amantadine is a medication that is useful in treating some symptoms of Parkinson's disease. It

Amantadine may cause greater amounts of dopamine to be released in the brain. ... It can help to reduce
dyskinesias, involuntary movements that may result from taking some Parkinson's medications.
This medication is used to treat movement disorders caused by Parkinson's disease. It does not
cure Parkinson's disease, but it may improve shakiness (tremor), muscle stiffness, loss of normal
movement.
Selegiline
Selegiline is an enzyme blocker (MAO inhibitor) that works by slowing the breakdown of certain
natural substances in the brain (neurotransmitters such as dopamine, norepinephrine, and serotonin).
Dizziness, stomach upset, trouble sleeping, and headachemay occur.

DRUGS FOR ALZIEHMAR’S DISEASE:

DRUG NAMES AND

BRANDS
Cholinestearse inhibitor- It is prescribed to treat mild-to-moderate and moderate-to-
severe AD.
Donepezil (aricept)
It works by preventing the breakdown of acetylcholine in the brain
Nausea, vomiting and diarrhea are its common side effects
Cholinestearse inhibitor- prescribed to treat mild-to-moderate ADA
It works by preventing the breakdown of acetylcholine and stimulates nicotinic
Galantamine (razadyne)
receptors to inc. the realease of Ach in the brain
Nausea, loss of appetite, vomiting and diarrhea are its common side effects
NMDA antagonist- prescribed to treat moderate-to-severe AD
Memantine (namenda) It works by blocking the toxic effects associated with excess glutamate and
regulates glutamate activation

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 Dizziness, headache and constipation are its common side effects

DRUGS OF MULTIPLE SCELROSIS

DRUGS NAMES
This medication is used to treat a certain type of multiple sclerosis (relapsing multiple
sclerosis-MS). It is not a cure for MS but it is thought to help by preventing immune
Fingolimod system cells (lymphocytes) from attacking the nerves in your brain and spinal cord. It
helps decrease the number of episodes of worsening and may prevent or delay disability.
Cough, headache, back pain, or diarrhea may occur.
Mitoxantrone is a chemotherapy drug that is used to treat multiple sclerosis (MS)
and certain types of cancer.It can lead to heart damage during therapy and even
Mitoxantrone some years later.
In MS: Immune cells damage the protective covering of nerves. Mitoxantrone
limits the ability of these cells to damage the protective nerve covering.
Dalfampridine is used to improve walking in people with multiple sclerosis (MS). It is
Dalfapridine a potassium channel blocker. It is thought to work by improving nerve conduction.
Trouble sleeping (insomnia), dizziness, nausea, and headache may occur.

ANAESTHETICS

Anaesthesia refers to the practice of administering medications either by injection or by

inhalation (breathing in) that block the feeling of pain and other sensations, or that produce a
deep state of unconsciousness that eliminates all sensations, which allows medical and surgical
procedures to be undertaken without causing undue distress or discomfort.
there are several types of anaethesia
1. General anaesthesia
2. Regional Anesthesia
3. Local anesthetics
4. sedation

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 Drugs For Anesthesia:
 Barbiturates. Amobarbital (trade name: Amytal) Methohexital (trade name: Brevital) Thiamylal
(trade name: Surital) ...
 Benzodiazepines. Diazepam. Lorazepam. Midazolam.
 Etomidate.
 Ketamine.
 Propofol.
Pharmacokinetics:
 All of the Anesthetics are well absorbed after oral administration. Peak levels are seen in
approximately 1to 2 hours.
Indications:
Local anaesthetics can be used alone or in combination with other types of anaesthetic agents
such as spinal or epidural anaesthetics.

 Local anaesthesia is given to reduce the stress associated with surgery, and to provide pain
relief after surgery.

 More commonly, it is used for pain caused by hemorrhoids, fissures, insect bites, and minor
burns. It is applied topically for these conditions.

 It is also indicated for vaginal, rectal and otological examinations, cystoscopy, and
catheterization.

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definition.html
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