PSYC211 Chapter 4 Notes
Psychopharmacology: The study of the effects of drugs on the nervous system and on behaviour.
Drug Effect: The changes a drug produces in an animal’s physiological processes and behaviour.
Sites of Action: The locations at which molecules of drugs interact with molecules located on or in cells
of the body, thus affecting some biochemical processes of these cells.
Pharmokinetics: The process by which drugs are absorbed, distributed within the body, metabolized,
Intravenous (IV) Injection: Injection of a substance directly into a vein.
Intraperitoneal (IP) Injection: Injection of a substance into the peritoneal cavity (the space that
surrounds the stomach, intestines, liver, and other abdominal organs).
Intramuscular (IM) Injection: Injection of a substance into a muscle.
Subcutaneous (SC) Injection: Injection of a substance into the space beneath the skin.
Oral Administration: Administration of a substance into the mouth so that it is swallowed.
Sublingual Administration: Administration of a substance by placing it beneath the tongue.
Intrarectal Administration: Administration of a substance into the rectum.
Inhalation: Administration of a vaporous substance into the lungs.
Topical Administration: Administration of a substance directly onto the skin or mucous membrane.
Intracerebral Administration: Administration of a substance directly into the brain.
Intracerebroventricular (ICV) Administration: Administration of a substance into one of the cerebral
Depot Binding: Binding of a drug with various tissues of the body or with proteins in the blood.
Albumin: A protein found in the blood; serves to transport free fatty acids and can bind with some lipid-
Dose-Response Curve: A graph of the magnitude of an effect of a drug as a function of the amount of
Therapeutic Index: The ratio between the dose that produces the desired effect in 50% of the animals
and the dose that produces toxic effects in 50% of the animals.
Afﬁnity: The readiness with which 2 molecules join together.
Tolerance : A decrease in the effectiveness of a drug that is administered repeatedly.
Sensitization: An increase in the effectiveness of a drug that is administered repeatedly.
Withdrawal Symptom: The appearance of symptoms opposite to those produced by a drug when the
drug is administered repeatedly and then suddenly no longer taken.
Placebo: An inert substance that is given to an organism in lieu of a physiologically active drug; used
experimentally to control for the effects of mere administration of a drug.
Antagonist: A drug that opposes or inhibits the effects of a particular neurotransmitter on the
Agonist: A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell.
Direct Agonist: A drug that binds with and activates a receptor.
Receptor Blocker: A drug that binds with a receptor but does not activate it; prevents the natural ligand
from binding with the receptor.
Direct Antagonist: A synonym for a receptor blocker. Non-competitive Binding: Binding of 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 interferes with the action of
the receptor; does not interfere with the binding site for the principal ligand.
Indirect Agonist: A drug that attaches to a binding site on a receptor and facilitates the action of 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 terminal button by means of an axoaxonic synapse; binds with the neurotransmitter
released by the presynaptic terminal button.
Acetyl-CoA: A cofactor that supplies acetate for the synthesis of acetylcoline.
Choline Acetyltransferase (ChAT): The enzyme that transfers the acetate ion from acetyl coenzyme A to
choline, producing the neurotransmitter acetylcholine.
Botulinum Toxin: An acetylcholine antagonist; prevents release by terminal buttons.
Black Widow Spider Venom: A poison produced by black widow spiders that triggers the release of
Hemicholinium: A drug that inhibits the uptake of choline.
Neostigmine: A drug that inhibits the activity of acetylcholinesterase.
Nicotinic Receptor: An ionotropic acetylcholine receptor that is stimulated by nicotine and blocked by
Muscarinic Receptor: A metabotropic acetylcholine receptor that is stimulated by muscarine and blocked
Atropine: A drug that blocks muscarinic acetylcholine receptors.
Curare: A drug that blocks nicotinic acetylcholine receptors.
Monoamine: A class of amines that includes indolamines, such as serotonin; and catecholamines, such
as dopamine, norepinephrine, and epinephrine.
Catecholamine: A class of amines that includes the neurotransmitters dopamine, norepinephrine, and
Dopamine (DA): A neurotransmitter; one of the catecholamines.
L-DOPA: The levorotatory form of DOPA; precursor of the catecholamines; often used to treat Parkinson’s
disease because of its effects as a dopamine agonist.
Nigostriatal System: A system of neurons originating in the substantia nigra and terminating in the
neostriatum (caudate nucleus and putamen).
Mesolimbic System: A system of dopaminergic neurons originating in the ventral tegmental area and
terminating in the nucleus accumbens, amygdala, and hippocampus.
Mesocortical System: A system of dopaminergic neurons originating in the ventral tegmental area and
terminating in the prefrontal cortex.
Parkinson’s Disease: A neurological disease characterized by tremors, rigidity of the limbs, poor
balance, and difﬁculty in initiating movements; caused by degeneration of nigrostriatal system.
AMPT: A drug that blocks the activity of tyrosine hydroxylase and thus interferes with the synthesis of the
Reserpine: A drug that interferes with the storage of monoamines in synaptic vesicles.
Apomorphine: A drug that blocks dopamine autoreceptors at low doses; at higher doses, blocks
postsynaptic receptors as well.
Methylphenidate: A drug that inhibits the reuptake of dopamine. Monoamine Oxidase (MAO): A class of enzymes that destroy the monoamines; dopamine,
norepinephrine, and serotonin.
Deprenyl: A drug that blocks the activity of MAO-B; acts as a dopamine agonist.
Chloropromazine: A drug that reduces the symptoms of schizophrenia by blocking dopamine D2
Norepinephrine (NE): One of the catecholamines; a neurotransmitter found in the brain and in the
sympathetic division of the autonomic nervous system.
Epinephrine: One of the catecholamines; a hormone secreted by the adrenal medulla; serves also as a
neurotransmitter in the brain.
Fusaric Acid: A drug that inhibits the activity of the enzyme dopamine-beta-hydroxylase and thus blocks
the production of norepinephrine.
Moclobemide: A drug that blocks the activity of MAO-A; acts as a noradrenergic agonist.
Locus Coeruleus: A dark coloured group of noradrenergic cell bodies located in the pons near the rostral
end of the ﬂoor of the fourth ventricle.
Axonal Varicosity: An enlarged region along the length of an axon that contains synaptic vesicles and
releases a neurotransmitter or neuromodulator.
Idazoxan: A drug that blocks presynaptic noradrenergic alpha-2 receptors and hence acts as an agonist,
facilitating the synthesis and release of NE.
Serotonin (5-HT): An indolamine neurotransmitter; also called 5-hydroxytryptamine.
PCPA: A drug that inhibits the activity of tryptophan hydroxylase and thus interferes with the synthesis of
Fluoxetine: A drug that inhibits the reuptake of 5-HT.
Fenﬂuramine: A drug that stimulates the release of 5-HT.
LSD: A drug that stimulates 5-HT2A receptors.
MDMA: A drug that serves as a noradrenergic and serotonergic agonist, also known as “ecstasy”; has
excitatory and hallucinogenic effects.
Glutamate: An amino acid; the most important excitatory neurotransmitter in the brain.
NMDA Receptor: A specialized ionotropic glutamate receptor that controls a calcium channel that is
normally blocked by Mg2+ ions; has several other binding sites.
AMPA Receptor: An ionotropic glutamate receptor that controls a sodium channel; stimulated by AMPA.
Kainate Receptor: An ionotropic glutamate receptor that controls sodium channels; stimulated by kainic
Metabotropic Glutamate Receptor: A category of metabotropic receptors that are sensitive to glutamate.
AP5 (2-Amino-5-Phosphonopentanoate): A drug that blocks the glutamate binding site on NMDA
PCP: Phencycliﬁne; a drug that binds with the PCP binding site of the NMDA receptor and serves as an
GABA: An amino acid; the most important inhibitory neurotransmitter in the brain.
Allylglycine: A drug that inhibits the activity of GAD and thus blocks the synthesis of GABA.
Muscimol: A direct agonist for the GABA binding site on the GABA-A receptor.
Bicuculline: A direct antagonist for the GABA binding site on the GABA-A receptor.
Benzodiazepine: A category of anxiolytic drugs; an indirect agonist for the GABA-A receptor.
Anxiolytic: An anxiety-reducing effect.
Introduction • A drug is an exogenous chemical not necessary for normal cellular functioning that signiﬁcantly alters
the functions of certain cells of the body when taken in low doses.
• Exogenous means it is NOT produced by the body.
• Things that MIMIC chemicals made in the body can count as drugs though.
• Low dosage is important, because anything in high doses can be toxic.
Principles of Psychopharmacology
• To be effective, drug must reach its site of action.
• Drug must enter body, and enter bloodstream to be carried to organ(s) on which they act.
• Then must leave bloodstream and come into contact with the molecules with which they interact.
• Once the drugs enter the body, they begin to be metabolized (broken down by enzymes) or
excreted by urine (or both). In time either disappear or become inactive fragments.
• Drugs that affect CNS are more important than those that effect PNS.
• Molecules of drugs must cross several barriers to enter body to ﬁnd site of action.
Routes of Administration
For lab animals, most common route of drug administration is injection.
• Fastest route is IV injection. Drug reaches brain within a few seconds. Disadvantages are increased
care/skill needed to do it.
• IP injection is almost as fast as IV. IP injection is most common route for small lab animals.
• IM injection, drug is absorbed into blood stream via small capillaries that supply the muscle. Good for
slow absorption when used with ephedrine (to constrict blood vessel and retard ﬂow of blood).
• SC injection is useful only if small amounts of drug are needed, because injecting lots would be painful.
Can do this by dissolving drug in oil, over time drug will leave deposit of oil (several days). Or can put a
pellet in a sealed capsule and implant in skin to administer very slowly.
• Oral is most common form of giving medicinal drugs to humans. Not good for lab animals. Some
chemicals can’t be given orally because stomach acid/digestive enzymes will destroy it, or won’t get
absorbed into blood stream.
Sublingual - drug is absorbed into bloodstream via capillaries that supply the mucous membrane that
lines mouth. Only used in humans.
• Intrarectal - rarely used with animals. Mostly used for drugs that might upset someone’s stomach.
• Inhalation - Nicotine, freebase cocaine, and pot usually smoked. Drugs to treat lung disorders often
used, inhaled as vapour/mist. Route from lungs to brain is short, so rapid effects in this way.
• Topical - steroid hormones are administered this way, and nicotine. Administering to mucous membrane
lining nasal passage also counts as topical (cocaine hydrochloride is used this way - snorting). This
route delivers drugs to brain very fast.
• Intracerebral - directly into brain.
• Intracerebroventricular (ICV) - to get widespread distribution, must pass blood brain barrier, so it will be
injected directly into cerebral ventricle, then it will get absorbed into brain tissue, where it will exert its
effects. Used rarely in humans, mostly used to give antibiotics to brain to treat certain infections.
Distribution of Drugs Within the Body
• Other than intracerebral/ICV, routes vary only in the rate at which the drug reaches the blood plasma.
• Several factors determine rate at which drug in bloodstream reaches site of action:
• Lipid solubility. • Blood brain barrier is a barrier only for water-soluble molecules, so lipid soluble ones pass
through cells that line capillaries in CNS and rapidly distribute in brain.
• Depot binding.
• Many drugs bind with various tissues in body or with proteins in blood (depot binding). As long
as drug molecules are bound to a depot, they can’t reach their site of action and can’t exert
their effects. One source of binding is albumin, which transports free fatty acids, but can also
bind with some lipid-soluble drugs. Depot binding can both delay and prolong effects of a drug,
by the speed of binding a