Pharmacology of Consciousness

1
Pharmacology of Consciousness

• Introductory Considerations

2
Basics of Neurotransmission

• Neural signals are electrical as they pass along
  a neuron
• The junction between one neuron and its target is
  a synapse. The synapse is literally a gap, even
  if a very small gap
• Neural signals are chemical as they go across the
  synapse

3
Synaptic Processes

• Neurotransmitters are created in neuron and
  stored in packets called vesicles
• Vesicles move to membrane and release their
  contents into synapse
• Transmitter molecules bind to receptor sites on
  post-synaptic membrane
• Transmitter is catalyzed, reabsorbed or degraded
  to remove its effect

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Drug Effects General Points

• Agonist
• A chemical that mimics the effects of a
  neurotransmitter
• Antagonist
• A chemical that blocks the effects of a
  neurotransmitter

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Agonists for Acetylcholine

• Increase release of ACh
• black widow spider venom
• Activate the receptor for ACh
• nicotine
• Prevent the breakdown of ACh
• physostigmine (from Calabar bean)

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Antagonists for Acetylcholine

• Prevent the release of ACh
• Botulin toxin
• Block the receptor for ACh
• Curare
• Break down ACh
• cholinesterase

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Neurotransmitters

• Small molecule transmitters
• Peptide neurotransmitters
• Transmitter gases
• Nitric oxide (NO)
• Carbon monoxide (CO)

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Small molecule neurotransmitters

• Acetylcholine ACh
• Amines
• Dopamine DA
• Epinephrine (Adrenalin) EP
• Norepinephrine (Noradrenalin) NE
• Serotonin (5-HT)
• Amino Acids
• Glutamate Glu
• Gamma-aminobutyric acid GABA
• Glycine
• Histamine

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Synthesis of Aminergics

• Tyrosine hydroxylase
• L-dopa
• Dopamine
• Epinephrine
• Norepinephrine

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Peptide Neurotransmitters

• Opioids
• enkephalin, endorphin
• Neurohypophyseals
• vasopressin, oxytocin
• Secretins
• GHR peptide
• Insulins
• Gastrins
• Somatostatins

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7 Types of Psychoactive Drugs

• Antianxiety agents
• Antipsychotic agents
• Antidepressants
• Mood stabilizers
• Narcotic analgesics
• Psychomotor stimulants
• Psychedelics and hallucinogens

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Antianxiety Agents Sedative Hypnotics(Minor
tranquilizers)

• Alcohol (ethanol)
• Barbiturates
• once called sleeping pills, now used for
  preliminary anesthesia
• Benzodiazepines
• Chlordiazepoxide (Valium, Librium)
• Meprobamate (Miltown, Equanil)Librium

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Antianxiety Agents Mechanism

• GABA receptor agonist
• Gamma aminobutyric acid is an inhibitory
  neurotransmitter
• Alcohol acts like GABA
• Benzodiazepines make GABA more effective
• Joint effects can be fatal

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Antipsychotic Agents(Major Tranquilizers)

• Phenothiazines
• Chlorpromazine (Largactile, Thorazine)
• Butryophenones
• Haloperidol (Haldol)

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Antipsychotic Agents Mechanisms

• Perhaps Dopamine Antagonists
• Both block dopamine D2 receptor
• Amphetamines aggravate schizophrenia
• Dopamine agonist
• Major Side Effect
• Tardive dyskinesia

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Antidepressant Agents

• MAO inhibitors
• Iproniazid (Marsilid)
• Tricyclic antidepressants
• Imipramine (Tofranil)
• Selective serotonin reuptake inhibitors (SSRI)
• Fluoxetine (Prozac)

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Antidepressant Agents Mechanisms

• Serotonin agonist (1 mechanism)
• MAO inhibitors
• prevent breakdown of serotonin
• Tricyclics and SSRIs
• prevent reuptake of serotonin

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Narcotic Analgesics

• Endogenous opiates
• Enkephalins
• Endorphins
• Exogenous opiates
• Morphine
• Codeine
• Oxycodone, hydrocodone

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Narcotic Sources
Opium Poppy
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Narcotic Analgesics Mechanisms

• Morphine receptor agonists
• Morphine binds to morphine receptor
• Antagonists block receptor
• Naloxone
• Naltrexone

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The MPTP Story

• In 1979, a graduate student attempted to
  synthesize meperidine, a synthetic opiate, and
  accidentally created MPTP
• When ingested, MPTP is metabolized in the brain
  to MPP
• MPP kills dopaminergic cells in the midbrain
  that project to the basal ganglia
• The result Parkinsons disease

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Psychomotor Stimulants

• Cocaine
• Amphetamine
• Methamphetamine
• Caffeine
• Nicotine

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Stimulant Sources
Cocaine
Nicotine
Coca plant
Tobacco plant
Caffeine
Coffee plant
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Stimulants Mechanisms

• Dopamine agonist
• Increased release of dopamine for pre-synaptic
  membrane
• Blocking of reuptake by dopamine transporter

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Psychedelics/Hallucinogens

• Minor psychodelics
• Cannabis
• Major Psychedelics
• Psilocybin (psilocybin mushroom)
• Mescaline (peyote cactus)
• LSD (synthetic form of ergot)

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Natural Psychedelic Sources
Psylocibin Mushroom
Peyote Cactus
Nutmeg
Marijuana Plant
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Psychedelic Alphabet Soup

• Tryptamines (removed by MAO)
• DMT (N,N Dimethyltryptamine)
• 5- Meo -DMT
• DPT (N,N Dipropyltryptamine)
• GHB (gamma hydroxybutyrate)
• Amphetamines
• MDMA (Ecstasy - Methylenedioxy -n-methylamphetamin
  e)

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Psychedelics Mechanisms

• Serotonin agonists
• Stimulate serotonin receptors
• Norepinephrine agonists
• mescaline
• Anandamide agonists
• THC
• Acetylcholine agonists