Drugs and NT

Addictive and psychotropic drugs: Psychoactive substances, more commonly known as psychoactive drugs, are substances that, when taken, have the ability to change an individuals consciousness, mood or thinking processes. They act on central nervous system on mechanisms that exist normally to regulate the functions of mood, thoughts, and motivations. It includes alcohol and other hypnotics and sedatives, nicotine, opioids, cannabis, cocaine, amphetamines and other stimulants, hallucinogens, and psychoactive inhalants. The common psychoactive substances are: 1. alcohol, 2. sedative/hypnotics, 3. nicotine, 4. opioids, 5. cannabis, 6. cocaine, 7. amphetamines and other stimulants, and 8. hallucinogens. Many drugs lead to physical dependence and lead to addiction and are called addictive drugs. 1. Alcohol: most of it is metabolized to acetyldehyde by alcohol dehydrogenase and other enzymes largely in the liver. Subsequently, acetaldehyde is converted to acetate by hepatic aldehyde dehydrogenase. Mode of axn: o Blocks glutamatergic NMDA receptors and activates GABA receptors---sedative effect of alcohol and impairment of memory during periods of intoxication. o Degenerative effect due to acetaldehyde- reacts with proteins, nucleotides, amines. Etc. o euphoric feeling experienced by some drinkers, results from a metabolite of ethanol in the brain. For example, acetaldehyde could form alkaloids 2. Seative/ hynotics: Eg:Benzodiazepines and barbiturates Mode: binding to a specific binding site on the GABA-A receptor complex, which facilitates the effects of GABA on the opening of the chloride channel 3. Nicotine : stimulants powerful agonist of several subpopulations of nicotinic receptors of the cholinergic nervous system. Nicotine enhances fast excitatory transmission855 and may sharpen memory Indirectly affect dopa receptors 4. cocaine amphetamines: psychostimulants acts as a monoamine transporter blocker, with similar affinities for dopamine, serotonin, and norepinephrine transporters. Euphoric feeling Amphetamines are stimulants of the central nervous system that produce increased alertness, arousal, energy, motor and speech activity, increased self-confidence and ability to concentrate, an overall feeling of well-being and reduced hunger 5. Opioids:

Opiate drugs are compounds that are extracted from the poppy seed + other symthetic and semi syn compounds with similar properties. Eg: morphine, heroine, enkephalins, endorphins and endomorphins Opiate receptors: The three major types (mu, delta, kappa) are all 7-helix receptors coupled to adenylate cyclase, K+ and Ca2+ channels, and the MAP kinase cascade Powerful analgesics Highly addictive

6. The hallucinogens are a chemically diverse class, but are characterized by their ability to produce distortions in sensations, and to markedly alter mood and thought processes eg: LSD, psilocybin, phenylethylamines like dimethoxy-4methylamphetamine (DOM) Act on serotonin systemLSD Refer paper: mechanism of addiction, same drug different axn,

NT: 1. Chemical molecules help in transmission of signal from one neuron to the other across the synapse 2. Major job: Relay, Amplify and Modulate Signals between a neuron and another neuron or a cell 3. Five important criteria: a synthetic mechanism exists within the presynaptic neuron; a mechanism of storage (in vesicles) is evident; the transmitter is released in proportion to the strength of the stimulus (frequency of firing); postsynaptic action of the transmitter has been demonstrated directly by microiontophoresis; and an efficient means for inactivation of the transmitter is present. 4. Applying the substance to a postsynaptic cell should mimic the effects caused by stimulating the presynaptic terminal 5. Neurotransmitter receptors mediate changes in membrane potential according to: The amount of neurotransmitter released 5 The amount of time the neurotransmitter is bound to receptors

1. Ach: Most abundant NT in Peripheral N.S. Also found in CNS Ester of choline and acetic acid synthesized from choline and acetyl CoA using enzyme cholineacetyl transferase(ChAT) which transfers acetyl group to choline

has has 2 types of receptors A. nicotinic receptors: Ionotropic a. agonist: is nicotine b. antagonist: is curare B. muscarinic receptors: metabotropic a. agonist: is muscarine

b. antagonist: antagonist: in atropine (deadly nightshade

PNS : Activates muscles , NMJ

CNS : associated with cholinergic system, excitatory action. ACh has a variety of
effects as a neuromodulator,

2.Damage to the cholinergic system in the brain has been suggested to play a role in the memory deficits associated with Alzheimer's Disease. Monoamines: Amino acid precursors precursors single amine group 2 groups Catecholamines catechol ring Indolamine indole ring Affected by many of same drugs Catecholamines: 1. Epinephrine 2. Norepi 3. Dopamine Catecholamine-containing neurons are found cortex and cerebellum regions Terminated by... 1. reuptake 2. monoamine oxidase oxidase MAO MAO

3. catecholOmethyltranferase COMT Adrenaline and noradrenaline stimulate smooth muscles throughout the body and have a hypertensive effect Their postsynaptic receptors are 7-helix transmembrane proteins Norepinephrine and dopamine are utilized in brain circuits which regulate all body functions, mood, emotions, and cognitive abilities Peripheral N.S. Sympathetic neuroeffector junction and Adrenal glands Central N.S. Hypothalamus and Locus coeruleus Alpha & Beta receptor subtypes NE & NE It also determines consciousness, sleep rhythms, attention, and vigilance Stimulants, including caffeine, cocaine and amphetamines act in a NE-increasing mode with temporary increase in psychic energy and a sense of well-being. They also influence the dopamine system Dopamine Only in central nervous system - mostly inhibitory system At least 5 DAR types: D1, D2 etc. ~ Indolamines:

The indolealkyl amine serotonin 2.Found in all mammalian brains and in invertebrates 3.serotonin-containing neurons being found in the raphe nuclei of the brainstem

4.Have both inhibitory and excitatory responses 5.Serotonin accumulating neurons are also found in the retina Serotonin is synthesized via tryptophan and 5- hydroxytryptophan 9.Within the pineal body of the brain and in the retina, serotonin is acetylated to N-acetylserotonin, which is then O-methylated to melatonin 1.14 distinct types of serotonin receptors 2.They are present in the heart, in gastrointestinal tissues, adrenal and other glands, and bone as well as in the brain
1.Serotonin and melatonin are evidently involved in maintenance of the 24-h circadian rhythm of the body 2.Melatonin influences the onset of puberty

GABAergic Major NT in brain inhibitory system Receptor subtypes GABA A controls Cl channel GABA B - controls K+ channel Precursor = glutamate L-glutamate is the major excitatory transmitter in the central nervous system. Responsible for nearly all of the very fast acting nerve impulses in the brain by increasing