Pharmacology of the central

nervous system

Dr. Maryam Mohammadzadeh Akın

 Neurotransmitters
• There are also neurotransmitters in the central nervous system, such as
the autonomic nervous system and the peripheral nervous system.

• Certain chemicals are used in the communication between the cells of

the central nervous system or between the central nervous system and
the endocrine system (neuro humoral communication), these
substances are called Neuroregulators.

• neuroregulators are divided into three groups as, neurotransmitters,

neuromodulators and neurohormones.
 Neurotransmitters

• They are responsible for the communication between two neurons in the central nervous
system.

• In synapses, they are secreted from the axon end (presynaptic end) and affect the
membrane of the other cell (postsynaptic membrane).
• They enable the message to be carried from the presynaptic end to the postsynaptic
membrane.
• The effect of these substances on the membrane is usually in the form of opening or
closing of ion channels as a result of activating their specific receptors

• The activities of neurotransmitters in the central nervous system end with re-uptake,
except for acetylcoline and histamine.
 Neurotransmitters
• The effect of neurotransmitters is terminated by reuptake or
metabolizing to the neuron.

• The effect of acetylcholine and histamine does not end with re_up
take. acetylcholine is broken down by acetyl choline asterase and
histamine broken down by histaminase enzyme.
Action potential is travelling down the neuron and massage get across from
presynapthic neuron to the postsynapthic neuron
Neurotransmitters
 Ion channels and toxins that block these
channels
• Local anesthetics block voltage-dependent sodium channels, apart
from that;
 Tetradotoxin
 Saxitoxin

• N type ca + 2 channels dependent on voltage

 Omega Conotoxin
• GABAA receptor (this receptor is an inhibitory receptor and causes the
entry of Cl- ion into the neuron, thus preventing convolution, picrotoxin
has no medical purpose because it causes convulsion, so we use this toxin
in laboratories and animals to create experimental epilepsy models.
( picrotoxin)
• Glycine

• This toxin, which blocks the entry of Cl into the cell by blocking the glycine
receptor, is the most powerful convulsant.
• strychnine (rat poison)

• Nicotinic Ach receptor

Bungarotoxins , this toxin paralyzes the skeleton muscles. Diaphragm paralyzes
and death occurs

Na + enters the neuron to secrete neurotransmitter from the neuron, then Ca + 2

enters, the neuron depolarizes, and releases neurotransmitters into the synaptic
cleft
 amine-like neurotransmitters

• Ach
• Dopamine
• Noradrenaline \ adrenaline
• Histamine
• Serotonin (5-HT)

• Neurotransmitters with amino acid structure (excitatory ones)

• Glutamate
• Aspartate
 amine-like neurotransmitters
• neurotransmitters with amino acid structure (inhibitors)
• GABA
• Glycine
 Dopamine
• It is found at the highest concentration in the nucleus accumbens and amygdala in the
basal ganglia and nigrostriatal pathway. The result of reduced dopamine in the
nigrostratal pathway is parkinson, because this is the pathway that provides motor
movements.

• The second place dopamine is found is the mesolimbic and mesocortical pathways.
The result of increasing dopamine in this pathway is schizophrenia.

• metabolized to homovalinic acid by COMT (Catechol-O-methyltransferase)

• increased dopamine in the human periphery and brain, nausea, hallucination

(schizophrenia) euphoria (addiction) also dopamine increased
 Noradrenaline
• Noradrenaline is most abundant in the brain, the locus cereleus in the
brainstem.

• Noradrenaline has breakdown products; metanephrine,

normetanephrine, vanilmandelic acid,

• But its metabolite in the sanrtal nervous system is 3-methoxy4-

hydroxyphenylglycol.
 Serotonin (5-HT)

• It is synthesized from L-tryptophan by the enzymes tryptophan hydroxylase (TOH) and L-

aromatic amino acid decarboxylase (AADC).

• L-tryptophan (AADC) & (TOH) Serotonin (5-HT)

• Serotonin (5-HT) is mostly found in raphe nucleus in the central nervous system.

• It is broken down into 5-hıaa (5-hydroxy indole acetic acid) by MAO A and aldehyde
dehydrogenase enzyme.

• Major depression occurs in serotonin deficiency.Serotonin excess causes anxiety disorders.

• Serotonin (5-HT) reduces appetite by stimulating the satiety center in the
medial hypothalamus.

• All receptors of serotonin are G protein coupled. The 5-HT3 receptor is

the ion channel. Atypical antipsychotics such as Clozapine, which are used
in the treatment of schizophrenia by antagonizing 5-HT2A and 2C
receptors, are proof that they play a role in the etiology of schizophrenia.
 Drugs that affect the serotonergic system
• Buspirone
• 5HT1A agonist (this receptor is the autoreceptor that inhibits serotononin secretion) so it is;
• anxiolytic

• Triptan
• 5HT1B / D agonist
• migraine attack

• Ondansetron
• 5-HT3 antiemetic (these drugs are given especially in nausea and vomiting due to anticancer drugs )
 Drugs that affect the serotonergic system

• Cisapride / Tegaserod
• 5-HT4 agonist
• Prokinetic (type of drug which enhances GIS motility by increasing the frequency or strength of contraction, but
without disrupting their rhythm).

• Ketanserin (ketanserin is a more selective antagonist of the 5-HT2A over the 5-HT2C receptor)
• 5-HT2 antagonist
• Antihypertensive
• It has been used to reverse pulmonary hypertension caused by Protamin (which in turn was administered to reverse the
effects of Heparin overdose)

• Methysergide
• 5-HT2 antagonist
• Migraine prophylaxis
• Benzodiazepines are the drugs most commonly prescribed by doctors
for anxiety patients. Because these drugs cause sedation, cause that
the person sleeps because of the sedation, and does not feel stress or
bad feeling like suffocated feeling because patient sleeps.

• Buspirone makes its anxiolytic effect without sedation

 Acetylcholine
• Acetylcholine has effects on learning and memory. even the amount of
Ach in the brain of Alzheimer patients decreased.

• Ach is most often found in nucleus basalis.

• Drugs that inhibit acetylcholine asterase enzyme in the central nervous

system; Drugs such as Tacrin, Donapezil, Rivastigmine, Galantamine
are used in Alzheimer's disease.
• The decrease in acetylcholine in the central nervous system causes
dementia and Alzheimer's disease.
• The increase of acetylcholine in the basal ganglia causes Parkinson's
disease.
 GABA (Gamma Amino Butyric acid)

• It is the most important inhibitory neurotransmitter in the central nervous

system.

• Synthesized from glutamate (glutamic acid) by gulutamic acid

decarboxylase.
• The effect of GABA in the synaptic cleft ends with reuptake.

• It is broken down by the GABA transaminase into succinic semialdehyde.

 GABA receptors
• GABA is the most important inhibitor of the central nervous system.

• It has three receptors, GABA A, GABA B and GABA C.

• GABAA and GABAc are ion channel receptors that introduce chlorine
ion into the cell,

• GABAB is the receptor that inhibits adenylate cyclase via Gi.

 GABA A receptor

• As a result of Cl- channel opening, it increases the size of the intracellular

negative charge, causing hyperplarization and leads to inhibition.

• GABA A receptor agonist is muscimol, and antagonist of GABA is Bicukulin.

• Benzodiazepines and barbiturates are GABA A agonist drugs.

• Picrotoxin and pentylenetetrazole are antagonists of the Cl-channel through the

GABA A receptor, creating analeptic and convulsive effects
• Picrotoxin and pentylenetetrazole are antagonists of the Cl-channel
through the GABA A receptor, creating analeptic and convulsive
effects. These toxins are used to induce experimental epilepsy in
animals.
 GABA B RECEPTOR
• The GABA B receptor is coupled with Gi.
• They are not affected by benzodiazepines and barbiturates.
• GABA B agonist drug Baclofen antagonist drug is phacolofen and
saclofen
 GABA C
• It is the ion channel receptor, selective to cl- ions. It is found in the
retina, medulla spinalis, superior culliculus and pituitary.
 Glycine
• The most important inhibitor in the medulla spinalis and brain stem is
glycine.

• It is an ion channel receptor with GABA-like chlorine channel activity.

• Strychnine inhibits glycine ion channels thereby preventing Cl entry

into the neuron and causing convulsions.
• If there is strychnine poisoning, the medication we will give are anti-
epileptic drugs (benzodiazepines, barbiturates).
 Glutamate and Aspartate
• It is the main excitatory neurotransmitter of the central nervous
system.

• Glutamate is responsible for 75 percent of the excitation in the brain.

 Glutamate receptors
• Ion channel receptors

• (N-methyl-D-aspartate) receptor, kainic acid receptor(KA), AMPA receptor

• NMDA receptor
• excessive stimulation of NMDA , AMPA receptor, kainic acid receptors
causes damage in the central nervous system.

• When the NMDA respirator is overstimulated, Ca2 + enters the cell and
causes necrosis in the neuron.
 Drugs that affect glutamate receptors
• Memantine (Alzheimer's treatment)
• Riluzole (ALS tedavisi)
• Mg
• Ketamine
• Phencyclidine (Phencyclidine induces experimental schizophrenia)
 Anandamide

• It is a substance derived from arachidonic acid.

• It is a lipid-structured neurotransmitter.
• Anandamide is the endogenous ligand of cannabinoid receptors to
which marihuana binds.
•Thank you