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Psychopharmacology
The Study of the effects of drugs on the nervous system and behavior
• Drugs: – Exogenous chemical (not produced by the body)
– Not necessary for normal functioning• Not a vitamin, mineral, protein, carbs…
– Alters the functions of certain cells (neurons)– when given in low doses (mg/kg)
Drug influence:Changes in physiological and behavioral processes of the organism
Action sites:Sites where the drug
1. Form of drug administration (how it is taken)
2. Drug fate in body
Principles of psychopharmacology include:
1. Forms of drug administration:
1. Intravenous injection2. Intraperitoneal injection3. Intramuscular injection4. Subcutaneous injection
5. Oral administration6. Sublingual administration
7. Intrarectal administration8. Inhalation9. Topical administration10. Intracereberal administration
Drugs get to the brain usually through the blood
2. Fate of drug
Depot Binding with Blood Albumin ProteinCan influence the rate at which the drug will reach the brain from the blood stream
Drug efficacy
Dose-response curve – describes the influence of a drug as a function of the dose administered
Multiple effects of drugs
(beneficial effects, and side effects)
The separation between the two curves serves as an measure for its safety
Therapeutic Index = LD50/ED50
LD – Lethal doseED – effective dose
Examples:Morphine (muscle relaxant) has a TI of 70Cocaine: 15Heroin: 6
Alcohol: 10 (but you usually vomit/pass out before reaching the lethal dose)
Drug effectiveness depends on:
Site of action
Affinity & kinetics
Number of times it was used:
Tolerance = Decrease in the efficiency of a drug
Sensitization = Increase in the efficiency of a drug
Once a drug enters the brain it may have one of two effects:
• Agonist – mimics/facilitates the post-synaptic effect
• Antagonist – inhibits/blocks the post synaptic effect
for a given neurotransmitter
Drugs can affect any stage in the process of synaptic transmission:
1) Production of neurotransmitter
2) Packing in vesicles and vesicle release
3) Binding to receptors
4) Neurotransmitter degradation and reuptake
Production of neurotransmitter
1. Precursor of neurotransmitter (Agonist):
DopamineL-DOPA serves as a precursor for the production of dopamine (used in Parkinson’s Disease)
GlutamateMSG (monosodium glutamate) – is a precursor of glutamate production
2. Inactivation of an enzyme needed for synthesis (Antagonist)
AMPT (Alpha-methyl-p-tyrosine) – blocks Tyrosine hydroxylase (Antagonist)
serotonin
p-chlorophenylalanine (PCPA) – is an inhibitor of Tryptophan hydroxylase
Storage and release of neurotransmitter
1. Preventing storage by inactivating vesicle transporter (Antagonist)Reserpine (blocks storage of norepinephrine, serotonin, and
dopamine in the presynaptic vesicles)
2. Enhancing storage in vesicles by inhibiting neurotransmitter breakdown
3. Stimulation of release from terminal button (Agonist)
Black widow spider venom (facilitates release of AcH)
4. Inhibition of release from terminal button (Antagonist)
Butulinium toxin (Botox) – blocks release of AcH
Post-synaptic receptors
• Direct agonists (competitive binding) – bind with receptor and activate it (mimic the effect of the neurotransmitter)– Examples: Nicotine, and Muscarine for AcH, LSD for
serotonin
• Direct antagonist (competitive binding) – bind with the receptor and do not activate it (receptor blockers)– Examples: Curare (blocks the nicotinic AcH receptor)– Atropene (blocks the muscarinic AcH receptor)– Caffeine (blocks adenosine receptors)
Indirect agonist (non-competitive binding): Binds on a different site than the neurotransmitter but mimics its effect
Indirect antagonist (non-competitive binding): Binds on a different site than the neurotransmitter and blocks its effect
A voltage and Neurotransmitter dependent channel
PCP (angel dust): Indirect antagonist
NMDA receptor (glutamate)
PCP (angel dust) – indirect antagonist
GABAa
Neurotransmitter dependent Cl- channel
Indirect Agonists
Reduce anxiety
Neurotransmitter degradation and reuptake
1. Blockers of re-uptake (agonists)Example: Cocaine is a seotonin-norepinephrine-dopamine reuptake inhibitor
Hemicholine – blocks reuptake of choline and serves as an AcH antagonistRitalin – inhibits reuptake of dopamine and norepinephrineAmphetamine (‘speed’) – inhibits reuptake of dopamineFluoxetine (Prozac) – serotonine reuptake inhibitor (SSRI)MDMA (‘Ecstasy’) – NE and Serotonin transporters run backwards
2. Blockers of neurotransmitter degradation (agonist):Example: Neostigmine inhibits AcH-Esterase (the enzyme that breaks AcH to Choline and Acetate) resulting in prolonged presence of AcH in synaptic cleft
Effects on pre-synaptic receptors
• AutoreceptorsStimulation
• Less release of neurotransmitter
Apomorphine (dopamine)