Chapter 4 Psychopharmacology Drug Medication? Heroin or - - PDF document

Chapter 4

Psychopharmacology

Psychopharmacology

• Drug

– Medication? – Heroin or cocaine? – An exogenous chemical not necessary for normal cellular functioning that significantly alters the function

• f certain cells of the body when taken in relatively

low doses

• Drug effect

– Changes of physiological process and behavior

• Site of action

– May only have effect on certain neurons at certain locations

Routes of administration

• Intravenous (IV), vein
• Intraperitoneal (IP) injection, abdominal wall
• Intramuscular (IM) injection
• Subcutaneous (SC) injection, beneath the skin
• Oral administration
• Sublingual administration, beneath the tongue
• Intrarectal administration
• Inhalation, lung
• Topical administration, absorbed by skin
• Intracerebral administration
• Intracerebroventricular (ICV) administration

• Depot binding

– Binding of a drug with various tissues

• f the body or with

protein in the blood

• Albumin

– A protein found in the blood; serves to transport free fatty acids and can bind with some lipid- soluble drugs

• Dose-response curve
• Affinity

– The readiness with which two molecules join together (compare)

• Tolerance

– A decrease in the effectiveness of a drug that is administered repeatedly

• Withdrawal symptoms
• Sensitization

– An increase in the effectiveness of a drug that is administered repeatedly

• Placebo effects

– An inerr substance that is given to an organism lieu of a physiologically active drug; used experimentally to control for the effects of more administration of a drug

• Antagonists

– A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell

• Agonists

– A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell

• Competitive binding: binding of a

drug to a site on a receptor interferes with the site for the principal ligand

– Direct agonist

• A drug that binds with and

activates a receptor

– Direct antagonist / receptor blocker

• A drug binds with a receptor

but does not activate it; prevents the natural ligand from binding with the receptor

• Noncompetitive binding: Binding
• f a drug to a site on a receptor;

does not interfere with the binding site for the principal ligand

• Indirect antagonist

– A drug that attaches to a binding site on a receptor and facilitates the action

• f the receptor; does not

interfere with the binding site for the principal ligand

• Presynaptic

heteroreceptor

– A receptor located in the membrane of a terminal button that receives input from another reminal button by means of an axoaxonic synapse; binds with the neurotransmitter released by the presynaptic terminal button

Acetylcholine

• Choline acetyltransferase (ChAT)

Functions and sites of effects

• A. Muscular

movements and autonomic nervous system

• B. In the brain

–

• 1. Dorsolateral

pons—REM sleep –

• 2. Basal forebrain—

activating the cerebral cortex and facilitating perceptual learning –

• 3. Medial septum—

electrical rhythms of the hippocampus and modulate its function

• Acetycholinesterase (AChE)

Two types of ACh receptors

• Nicotinic receptor

– Ionotropic, fast, muscle fibers

• Muscarinic receptor

– Metabotropic, slow, dominant in CNS

Related Drugs of ACh

+

Muscarine Stimulate muscarinic receptors Muscle paralysis atropine curare nicotine neostigmine hemicholinium Black widow spider venom Botulinum toxin

• prevent

Release

+

stimulate Receptor Deconstructi

• n enzyme

(AChE) Reuptake of choline

• block
• Block muscarinic

receptors

• Block nicotinic

receptors

+

Stimulate nicotinic receptors

+

deactivate

Monoamine

• Classification

– Catecholamine

• Dopamine, Norepinephrine,

Epinephrine

• Catecholamine Synthesis

– L-DOPA---Dopamine--- Norepinephrine (NE)

– Indolamines

• Serotonin

Dopamine

• Both excitatory and

inhibitory

–

• 1. Nigrostriatal system—

substantia nigra to caudate nucleus and putamen— control of movement (Parkinson’s disease) –

• 2. Mesolimbic system—

ventral tegmental area to limbic system (amygdala and hippocampus)— reinforcing and rewarding (drug addiction) –

• 3. Mesocortical system—

ventral tegmental area to prefrontal cortex—short- term memory, planning and strategy.

• Receptors, D1 and D2

Related Drugs of Dopamine

+

Stimulate release Amphetamine, cocaine, methylphenidate inhibit Reuptake Alleviate schizophrenia Alleviate Parkinson’s disease deprenyl chlorpromazine High dose of apomorphine Low dose of apomorphine reserpine AMPT L-DOPA

+

facilitate Synthesis

• inhibit

Deconstructi

• n enzyme

(MAO) Post- synaptic receptor Autoreceptor Storage in vesicles

• inhibit

+

destroy

• inhibit

+

activate

• activate

Norepinephrine (NE)

• Autonomic nervous

system

• Final step of

synthesis: Domapine— norepinephrine

• ccurs inside the

vesicles

• Release through

axonal varicosities rather than terminal buttons

• Originating site:

Locus coeruleus in dorsal pons— increase in vigilance

• All adrenergic

receptors are metabotropic, α1, α2, β1, β2

• Both excitatory and

inhibitory effects.

Related Drugs of Norepinephrine

• Same with Dopamine

reserpine inhibit Storage in vesicles Stimulate release, same as Dopamine Amphetamine MDMA idazoxan moclobemide Fusaric acid

• inhibit

synthesis

+

block Deconstructi

• n enzyme

(MAO-A) Reuptake Autoreceptor

+

block

+

inhibit

Serotonin

• Mood, eating,

sleep, arousal, pain, dreaming

• Originated from

Raphe nuclei and projects to basal ganglia and hippocampal formation

• Released from

varicosities rather than terminal buttons

• At least 9 types
• f receptors

Related Drugs of Serotonin

+

LSD stimulate Receptor

• Same with Dopamine

reserpine inhibit Storage in vesicles

• PCPA

inhibit synthesis Stimulate releasing Treatment of obesity Treatment of depression, anxiety disorder and OCD MDMA fenfluramine Fluoxetine (Prozac)

+

inhibit Reuptake

+

inhibit

+

inhibit

Amino Acids

• The most common

neurotransmitters in CNS

– Glutamate (direct excitatory in brain and spinal cord) – Gamma-aminobutyric acid (GABA) (direct inhibitory in the brain) – Glycine (direct inhibitory in spinal cord)

• Direct excitatory/inhibitory

role

– Independent of receptors, suggesting a general modulating role before the evolution of receptor molecules.

Glutamate

• Four major receptors
• Ionotropic

– NMDA receptor – AMPA receptor – Kainate receptor

• Metabotropic receptor

– Metabotropic glutamate receptor

NMDA receptor of Glutamate

• 6 binding sites,

sodium and calcium channels—EPSP and second messenger

• Required conditions

– Glutamate – Glycine – Removal of magnesium-- depolarization

• Modulations

– Zinc ion (-) – Polyamine (+) – PCP (-)

• Both voltage and

neurotransmitter- dependent ion channel

Related Drugs of Glutamate

+

NMDA Stimulate NMDA receptor

+

Kainate acid Stimulate kainate receptor AP5 AMPA

+

Stimulate AMPA receptor receptor

• Blocks NMDA

receptor

GABA receptor

• 5 binding sites
• Stimulating:

– barbiturate, – Steroid site, – Benzodiazopine

• Inhibiting:

– Picrotoxin

• Ionotropic receptor
• r metabotropic?
• Voltage or

neutrotransmittor dependent Chloride channel?

• Excitatory or

inhibitory?

Related Drugs of GABA

+

calming effect barbiturate stimulate

• allylglycine

inhibit synthesis

+

Tranquilizing drugs, reduce anxiety, sleep medication Benzodiazepine Diazepam (Valium) Chlordiazepoxide (Librium) stimulate

• direct

bicuculline block direct Picrotoxin muscimol

+

stimulate receptor

• inhibit

Glycine

• Inhibitory neurotransmitter in the spinal cord
• Ionotropic receptor controlling a chloride

channel

• Strychnine blocks glycine receptor (-)
• Stychnine

block Receptor

Neuropeptides and meuromodulators

• General characteristics of

neuropeptides and neuromodulators

• 1. Larger molecular

weight

• 2. Slower-acting (minutes,

hours)

• 3. Can act in concert with

a neurotransmitter

• 4. Like neurotransmitters,

there is more than one receptor subtype, and the response is tissue-specific

Peptides

• Neurotransmitter: Endogenous opiods
• Receptor: Opiate receptor
• Effects

– Analgesia – Inhibits defensive response such as fleeing and hiding – Reinforcement (addiction)

• Naloxone

inhibit

+

Opiates (morphine, heroin, etc) stimulate Receptor

Lipids

• Neurotransmitter: anandamide
• Metabotropic receptors
• Effects

– Analgesia and sedation, stimulate appetite, reduce nausea, reduce symptom of motor disorder – Interferes with concentration and memory, alter visual and auditory perception and perception of the passage of time

+

MAFP inhibit Deconstructi

• n enzyme

(FAAH)

+

AM1172 block reuptake

+

THC stimulate

• Rimonabant

block receptor

Nucleosides

• Sugar molecule bound with a

purine or pyrimidine base

• Neuromodulator: adenosine
• Metabotropic receptors with

potassium channels

• Effects:

– Dilate blood vessel and bring

• xygen to cells

– Inhibitory, control of sleep, increase during wakefulness and decrease during sleep

• Caffeine, block receptor (-),

excitatory effects

• Caffeine

block Receptor

Soluble gases

• Nitric oxide (NO) one nitrogen and one oxygen atom
• Control of muscle of intestine wall; Dilate blood vessel

to become metabolically active

• Produced in several regions of a nerve cell, including

dendrites, release as soon as produced, no vesicles/impulse involved

• L-NAME deactivate the enzyme that involves in the

synthesis of NO, (-)

• L-NAME

inhibit Synthesis

brain Excitatory amino acid Glutamate Spinal cord Inhibitory amino acid Glycine Caffeine sleep Nucleosid es adenosine Analgesia and sedation, perception distortion Lipids anandamide Addiction to

• piates

Painkiller, inhibit defense, reinforcement peptides Enkephalins (Opioids) Inhibitory Excitatory & Inhibitory Excitatory & Inhibitory Excitatory & Inhibitory Excitatory & Inhibitory Postsynaptic effect Related diseases Functions Originated location Type Paralysis muscle movement, REM sleep, Memory, learning Dorsal lateral pons Basal forebrain Medial septum Acetic acid Acetylcholine (ACh) Parkinson’s disease, schizophrenia, depression Motor reward, planning Substantia nigra Ventral tegmental Amine Dopamine Dilate blood vessel Gas Nitric oxide (NO) Anxiety disorder Anxiety level brain amino acid GABA Depression, OCD, anxiety,

• besity

Mood, sleep, pain, appetite Raphe nuclei Amine Serotonin Depression Increase vigilance, heighten mood Locus coeruleus Amine Norepinephrine