PSYCH 415--Psychopharmacology and Neurotransmitters

drug - an exogenous chemical not necessary for normal cellular functioning that significantly alters the functions of certain cells in the body (the nervous system is of particular interest in psychopharmacology) when taken in relatively low doses (Carlson)

drug action - refers to how the drug alters the functioning of cells in the body (esp. the nervous system) physiologically or molecularly; e.g., reuptake inhibition, facilitation of neurotransmitter release, receptor blockade, direct receptor stimulation (any alteration of one of the steps involved in synaptic transmission would be considered a drug action)

site of action - refers to where the cells are (or the type of cells) that are altered; e.g., the site of action of cocaine is at dopamine synapses

drug effect - refers to the behavioral, mental, or outwardly observable physiological changes produced by the drug; e.g., analgesia, lowered body temperature, activation of the EEG, arousal, euphoria, hallucinations, sleep, change in blood pressure

routes of drug administration

  1. intravenous injection (IV) - injection directly into a vein; results in very fast uptake of drug; most accurate dosing
  2. intraperitoneal injection (IP) - into the gut or peritoneal cavity; fairly fast uptake and reliable dosing; most often used with small experimental animals such as rats and mice
  3. intramuscular injection (IM) - into a large muscle, e.g., in the upper arm or buttocks; rapidity of uptake and reliability of dosing is variable
  4. subcutaneous injection (SC) - under the skin; useful only for small injections; rapidity of uptake and reliability of dosing are variable
  5. oral administration - by mouth; most common way to give drugs to humans (but rarely used with experimental animals, which just spit them out); least reliable way to get accurate dosing; will not work with drugs that are destroyed by stomach acid or digested by enzymes in the stomach (e.g., peptides such as insulin)
  6. sublingual administration - under the tongue
  7. intrarectal administration - by rectal suppository
  8. inhalation - by inhalation of a gas directly into the lungs; very rapid uptake and rapid delivery to the brain
  9. topical application - applied to the skin or mucus membranes (e.g., in the nose)
  10. intracerebral administration - directly into brain tissue (used most often experimentally, but some drugs--such as antibiotics--that do not cross the blood-brain barrier must be administered this way)

therapeutic index - the ratio of the dose of a drug that causes toxic side effects 50% of the time and the dose that causes the desired therapeutic benefit 50% of the time

    TI = LD50 / ED50

  • drugs that have a low TI are considered more dangerous because it is relatively easy to overdose (the toxic dose is not much more than the therapeutic dose) - e.g., barbariturates
  • drugs that have a high TI are considered safer because it is relatively difficult to overdose (the toxic dose is several times the therapeutic dose - e.g., benzodiazepines

neurotransmitters

  1. acetylcholine
    1. first to be discovered due to its effect on the heart
    2. two kinds of receptors - nicotinic and muscarinic
    3. neuromuscular junction - excitatory on voluntary (skeletal) muscle fibers
    4. autonomic nervous system - e.g., innervation of the heart (inhibitory)
    5. in the brain (mostly muscarinic)
      1. learning and memory (depleted in Alzheimer's disease)
      2. REM sleep
      3. general activation of the cortex
    6. pharmacology
      1. nicotine - a receptor stimulator at nicotinic receptors ("agonist")
      2. curare - a receptor blocker at nicotinic receptors ("antagonist")
      3. alpha-bungarotoxin - an irreversible antagonist (from the venom of the banded krait)
      4. botulinum toxin - blocks release
      5. black widow spider venom - stimulates release
      6. various insecticides - acetylcholinesterase inhibitors (irreversible)
      7. neostigmine - used to treat diseases of the motor endplate, AChE inhibitor
  2. GABA
    1. primary inhibitory neurotransmitter in the CNS, esp. in the brain
    2. biosynthesized from glutamate (an amino acid) and inactivated enzymatically
    3. chemical structure (don't memorize this!) - COOHCH2CH2CH2NH2
    4. two receptor types - GABAA and GABAB
    5. pharmacology
      1. tranquilizers - barbiturates, benzodiazepines, and alcohol (agonists)
      2. convulsants - bicuculine, picrotoxin, Metrazol (once used in convulsive therapy)
      3. date rape drugs
        1. "roofies" (Rohypnol, a benzodiazepine)
        2. GHB - gamma-hydroxybutyrate, COOHCH2CH2CH2OH
  3. glycine
    1. a simple amino acid, inhibitory in the spinal cord and lower brainstem
    2. pharmacology - fortunately, there are few drugs that influence glycine
      1. tetanus toxin - blocks release (antagonist)
      2. strychnine - causes convulsions that are brought on by sensory stimuli (used as a rat poison)
  4. glutamate (glutamic acid)
    1. an amino acid, the primary excitatory neurotransmitter in the CNS
    2. there are at least five types of receptors, including the NMDA receptor
  5. catecholamines - one of the two primary categories of monoamine neurotransmitters
    1. dopamine (DA), norepinephrine (NE), and epinephrine (E, aka adrenaline)
    2. biosynthesis - from the amino acid tyrosine, to DOPA, to DA, to NE, to E
    3. inactivated by reuptake and by MAO
    4. cell bodies - locus coeruleus (NE), substantia nigra (DA), and ventral tegmental area (DA)
      1. autonomic nervous system - emotional arousal (NE)
      2. reticular formation - arousal, vigilance (NE)
      3. limbic system - emotion, motivation, reward (NE and DA)
      4. basal ganglia - modulation of voluntary movement (DA, lost in Parkinson's disease)
    5. receptor types - alpha and beta for NE, D1-D5 for DA
    6. pharmacology
      1. stimulants - amphetamines, cocaine (reuptake inhibitors)
      2. antidepressants (tricyclics) - NE reuptake inhibitors
  6. indoleamines - the other category of monoamines
    1. serotonin (5-HT) and melatonin
    2. biosynthesis - from the amino acid tryptophan
    3. inactivated by reuptake and by MAO
    4. cell bodies - in the raphe nuclei
      1. limbic system - mood
      2. reticular formation - sleep
      3. cortex - esp. sensory cortex
      4. pain areas in the lower brainstem
    5. pharmacology
      1. antidepressants - SSRIs
      2. hallucinogens - LSD, DMT, psilocybin, etc.
  7. neuropeptides - e.g., the endorphins

neuromodulation vs. neurotransmission

Return to PSYC 415 Main Page