Psychopharmacology -...

Chapter 4

Psychopharmacology

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Psychopharmacology

Psychopharmacology:• The study of the effects of drugs on the nervous

system and on behavior.

Drug effects:• The changes a drug produces in an animal’s

physiological processes and behavior.

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.

Principles of PsychopharmacologyPharmacokinetics

Pharmacokinetics:• The process by which drugs are absorbed,

distributed within the body, metabolized, and excreted.

Principles of PharmacologyRoutes of Administration

Intravenous (IV) injection:• Injection of a substance directly into a vein.

Intraperitoneal (IP) injection:• The 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

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 by placing itdirectly 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 ventricles.

Principles of PharmacologyDrug Effectiveness

Dose-response curve:• A graph of the magnitude of an effect of a drug

as a function of the amount of the drug administered.

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.

Principles of PharmacologyEffects of Repeated Administration

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.

Principles of PharmacologyEffects of Repeated Administration

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.

Principles of PharmacologyPlacebo Effects

Placebo:• An inert substance given to an organism in lieu of

a physiologically active drug; used experimentally to control for the effects of mere administration of a drug.

Sites of Drug Action

Antagonist:• A drug that opposes or inhibits the effects of a

particular neurotransmitter on the postsynaptic cell.

Agonist:• A drug that facilitates the effects of a particular

neurotransmitter on the postsynaptic cell.

Sites of Drug ActionEffects on Receptors

Direct agonist:• A drug that binds with an 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:• Synonym for a receptor blocker.

Noncompetitive 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 of 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 of the principal ligand.

Neurotransmitters and NeuromodulatorsAcetylcholine

The first transmitter to be discovered.

The primary neurotransmitter secreted by the efferent axons of the central nervous system.

All muscular movement is accomplished by the release of acetylcholine.

Appears to be involved in regulating REM sleep, perceptual learning, and memory.

Botulinum toxin:• An acetylcholine antagonist; prevents release by

terminal buttons.

Black widow spider venom• A poison produced by the black widow spider

that triggers the release of acetylcholine.

Neostigmine:• A drug that inhibits the activity of

acetylcholinesterase.

Nicotinic receptor:• An ionotropic acetylcholine receptor that is

stimulated by nicotine and blocked by curare.

Muscarinic receptor:• A metabotropic acetylcholine receptor that is

stimulated by muscarine and blocked by atropine.

Atropine:• A drug that blocks muscarinic acetylcholine

receptors .

Curare:• A drug that blocks nicotinic acetylcholine

receptors.

Neurotransmitters and NeuromodulatorsMonoamines

Catecholamines• Dopamine (DA)• Norepinephrine (NE)• Epinephrine

Indolamines• Serotonin (5-HT)

Neurotransmitters and NeuromodulatorsMonoamines

Monoamine:• A class of amines that includes indolamines such

as serotonin and catecholamines such as dopamine, norepinephrine, and epinephrine.

Indolamines• Serotonin (5-HT)

Neurotransmitters and NeuromodulatorsMonoaminesDopamine

Dopamine:• A neurotransmitter; one of the catecholamine.

• Produces both excitatory and inhibitory postsynaptic potentials.

• Implicated roles in movement, attention, learning, reinforcing effects of abused drugs.

• Synthesized from tyrosine that we obtain from our diet.

L-Dopa:• The levorotatory form of DOPA; the precursor of

the catecholamines; often used to treat Parkinson’s disease because of its as a dopamine agonist.

Nigrostriatal system:• A system of neurons originating in the substantia

nigra and terminating in the neostriatum (caudate nucleus and putamen of the basal ganglia); appears to play a role in the control of movement.

Mesolimbic system:• A system of dopaminergic neurons originating in

the ventral tegmental area and terminating in the nucleus accumbens, amygdala, and hippocampus; appears to play a role in the reinforcing effects of drugs that are commonly abused.

Mesocortical system:• A system of dopaminergic neurons originating in

the ventral tegmental area and terminating in the prefrontal cortex; appears to influence formation of short-term memories, planning, and preparing strategies for problem solving.

Parkinson’s Disease:• A neurological disease characterized by tremors,

rigidity of the limbs, poor balance, and difficulty in initiating movements; caused by degeneration of the nigrostriatal system; Parkinson’s disease has been treated with L-DOPA.

AMPT:• A drug that blocks the activity of tyrosine

hydroxylase and thus interferes with the synthesis of the catecholamines.

Reserpine:• A drug that interferes with the storage of

monoamines in synaptic vesicles; serves as a monoamine antagonist.

Apomorphine:• A drug that blocks dopamine autoreceptors at

low doses; at high doses blocks postsynaptic receptors as well.

Methylphenidate:• A drug that inhibits the reuptake of dopamine;

also known as “Ritalin”; used to treat children with attention deficit disorder.

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.

Chlorpromazine:• A drug that reduces the symptoms of

schizophrenia by blocking dopamine D2receptors.

Clozapine:• A drug that reduces the symptoms of

schizophrenia, apparently by blocking dopamine D4 receptors.

Neurotransmitters and NeuromodulatorsMonoaminesNorepinephrine (NE)

Norepinephrine is synonymous with noradrenaline.

Found in neurons of the brain and the autonomic nervous system.

Almost every region of the brain receives input from noradrenergic neurons.

Implicated to play central role in vigilance or attentiveness to events in the environment.

Norepinephrine:• One of the catecholamines; a neurotransmitter

found in the brain and in the sympathetic division of the autonomic nervous system.

Epinephrine:• One of the catecholamies; a hormone secreted

by the adrenal medulla; serves as a neurotransmitter in the brain.

Fusaric acid:• A drug that inhibits the activity of the enzyme

dopamine-ß-hydroxylase and thus blocks the production of norepinephrine.

Locus coeruleus:• A dark-colored group of noradreneric cell bodies

located in the pons near the rostral end of the floor of the fourth ventricle.

Neurotransmitters and NeuromodulatorsMonoaminesSerotonin (5-HT)

Serotonin:• Serotonin is an indolamine neurotransmitter; also

called 5-hydroxytryptamine (5-HT); thought to play a role in the regulation of mood, the control of eating, sleep, dreaming, and arousal; also thought to be involved in the regulation of pain.

• PCPA:A drug that inhibits the activity of tryptophanhydroxylase and thus interferes with the synthesis of 5-HT.

• Fluoxetine (Prozac):A drug that inhibits the reuptake of 5-HT.

• Fenfluramine:A drug that stimulates the release of 5-HT; used as an appetite suppressant.

• LSD:Lysergic acid diethylamideThis drug produces distortions of visual perceptions.A drug that stimulates 5-HT2a receptors.

Neurotransmitters and NeuromodulatorsAmino Acids

The most common amino acid transmitters are:

• Glutamate

• Gamma-amino-butyric acid (GABA)

• Glycine

Neurotransmitters and NeuromodulatorsAmino AcidsGlutamate

Glutamate:• An amino acid; the most important excitatory

neurotransmitter in the brain.

NMDA:• A drug that serves as a noradrenergic and

serotonergic agonist

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 and blocked by CNQX; the most common glutamate receptor.

Kainate receptor:• An ionotropic glutamate receptor that controls a

sodium channel; stimulated by kainic acid and blocked by CNQX.

Metabotropic glutamate receptor:• A category of metabotropic receptors sensitive to

glutamate.

AP5:• A drug that blocks the glutamate binding site on

NMDA receptors

Phencyclidine (PCP):• A drug that binds with the PCP binding site of the

NMDA receptor and serves as an indirect antagonist of glutamate.

• Behavioral symptoms include altered body image, feelings of isolation and sadness, cognitive disorganization, apathy, hostility euphoria and dreamlike states.

Neurotransmitters and NeuromodulatorsAmino AcidsGABA

GABA:• An amino acid; the most important inhibitory

neurotransmitter in the brain and spinal cord.

Neurotransmitters and NeuromodulatorsAmino AcidsGABA

Benzodiazepine:• A category of anxiolytic drugs; an indirect agonist

for the GABAA receptor.

Anxiolytic:• An anxiety-reducing effect.

Neurotransmitters and NeuromodulatorsAmino AcidsGlycine

Glycine:• An amino acid; an important inhibitory

neurotransmitter in the lower brain stem and spinal cord.

Strychnine:• A direct antagonist for the glycine receptor.

Neurotransmitters and NeuromodulatorsPeptides

Neurons of the central nervous system release a large variety of peptides.

A neuron manufactures both the polypeptides and the enzymes that it needs to break them apart.

Synthesis takes place in the soma and they are delivered to the terminal buttons by axoplasmictransport.

Most peptides appear to serve as neuromodulators, some act as neurotransmitter.

Neurotransmitters and NeuromodulatorsPeptides

Endogenous opioid:• A class of peptides secreted by the brain that act

as opiates; drugs that effect opioid receptors reduce pain.

Enkephalin:• One of the endogenous opioids.

Naloxone:• A drug that blocks opioid receptors.

Neurotransmitters and NeuromodulatorsLipids

Cannabinoid:• A lipid; an endogneous ligand for receptors that

bind with THC, the active ingredient in marijuana.

Anandamide:• A lipid; the endogenous ligand for receptors that

bind with THC, the active ingredient of marijuana.

Neurotransmitters and NeuromodulatorsLipids

Adenosine:• A nucleoside; a combination of ribose and

adenine; serves as a neuromodulator in the brain.

Caffeine:• A drug that blocks adenosine receptors.

Neurotransmitters and NeuromodulatorsSoluble Gases

Nitric oxide (NO):• A gas produced by cells in the nervous system;

used as a means of communication between cells.

Psychopharmacology -...

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