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Drugs
Outline
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Neurotransmitters
Agonists and Antagonists
Cocaine & other dopamine agonists
Alcohol & its effects / Marijuana & its effects
Synthetic & Designer Drugs: Ecstasy
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Classes of Neurotransmitters
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•  6 basic classes of NT: Peptides,
Gases, Purines, Acetylcholine,
Monoamines, and Amino Acids
Neurotransmitters
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Glutamate: general excitatory neurotransmitter
GABA: general inhibitory neurotransmitter (Cl-)
Substance P: incoming pain signals
Endorphins: pain management
Serotonin (5-HT): sleep & mood
Dopamine (DA): pleasure center & movement
Norepinephrine (NE): sympathetic nervous system
(induces aroused, heightened state)
•  Acetylcholine (ACh): parasympathetic nervous
system (induces calm, resting state) & motor system
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Synthesis of NTs
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•  Enzymes modify
basic chemicals
Synthesis of Catecholamines
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•  Phenylalanine (dietary nutrient)
•  PKU – Phenylketonuria – genetic
deficit of enzyme to metabolize
phenylalanine = mental retardation
•  Metabolized to Tyrosine
•  Enzymes modify:
–  Tyrosine → Dopa
–  Dopa → Dopamine
–  Dopamine → Norepinephrine
–  Norepinephrine → Epinephrine
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Synaptic events
Outline
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Neurotransmitters
Agonists and Antagonists
Cocaine & other dopamine agonists
Alcohol & its effects / Marijuana & its effects
Synthetic & Designer Drugs: Ecstasy
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Agonists
•  A drug which
– stimulates the effects of a particular
neurotransmitter
– or acts to enhance the transmitter’s
effect.
Agonists
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Antagonists
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•  A drug which
inhibits or
counteracts the
effects of a
particular
neurotransmitt
er
Drug Actions at the Synapse
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Drugs working at Dopamine 13
Synapse
Norepinephrine (NE)
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•  Activates fight or
flight resources
•  Depression
associated with
norepinephrine
depletion
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Serotonin (5-HT)
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•  Reuptake or
monoamine oxidase
deactivates
•  Important in sleep
regulation,
depression, & mood
disorders
Gamma-aminobutyric Acid (GABA)
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•  Main effect is to inhibit
action of other neurons
•  Lower levels
associated with anxiety
or panic attacks
•  decreased levels in
Huntington's disease
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Outline
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Neurotransmitters
Agonists and Antagonists
Cocaine & other dopamine agonists
Alcohol & its effects / Marijuana & its effects
Synthetic & Designer Drugs: Ecstasy
Dopaminergic System
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•  VTA – ventral tegmental
area
–  Reward, motivation,
planning
•  Substantia Nigra
–  Motor control
•  Parkinson's disease
associated with
dopamine depletion
•  Also associated with
schizophrenia
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Cocaine
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•  Cocaine blocks the reuptake of dopamine
•  Dopamine Build-up = pleasure feeling in the nucleus
of accumbens & heightened arousal / alertness
Cocaine blocks the recycling of dopamine
everywhere in the CNS
•  In the areas that control your breathing and heart rate
dopamine increases activity resulting in heart attacks
and loss of breathing control.
Overstimulation can kill neurons.
Excess dopamine can produce psychosis.
Drug Video
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http://www.youtube.com/watch?v=4OS2C4NemJI
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Ritalin
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•  Blocks DA uptake gradually
•  Leads to increased concentration
Outline
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Neurotransmitters
Agonists and Antagonists
Cocaine & other dopamine agonists
Alcohol & its effects / Marijuana & its effects
Synthetic & Designer Drugs: Ecstasy
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The Effects of Alcohol
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•  Alcohol is very fat-soluble
–  easy access through the blood-brain barrier
–  interfere with the structure of the cell membrane &
receptors in the membrane
•  RESULT: inhibits Na+ transport into all neurons
•  The effects of alcohol seen in all systems - motor,
vision, cognitive, etc. – nonspecific to a NT
The Effects of Alcohol
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•  Alcohol impairs cognitive judgment so that
people unintentionally hurt or kill themselves.
•  Alcohol can reduce breathing and heart rate so
much that the processes stop.
•  Large amounts and chronic use of alcohol can
damage neurons so that they die.
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Outline
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Neurotransmitters
Agonists and Antagonists
Cocaine & other dopamine agonists
Alcohol & its effects / Marijuana & its effects
Synthetic & Designer Drugs: Ecstasy
THC – Marijuana
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•  Endogenous NTs for cannabinoid receptors:
–  Anandamine:
•  inhibits the pre-synaptic release of glutamate in
hippocampal neurons (↓LTP)
•  inhibits the autonomic nervous system:
relaxation, hypothermic, ↓ ocular pressure
•  analgesic effects in the spinal cord
–  2-AG:
•  inhibits LTP in hippocampus and suppresses
pain sensations in the spinal cord
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Cannabinoid Receptor Density
•  Black labels CB receptors: high density in
cerebellum, cortex, basal ganglion, & hippocampus
Outline
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Neurotransmitters
Agonists and Antagonists
Cocaine & other dopamine agonists
Alcohol & its effects / Marijuana & its effects
Synthetic & Designer Drugs: Ecstasy
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What is Ecstasy?
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•  Synthetic derivative of methamphetamine
Ecstasy - mimics both dopamine30
& serotonin neurotransmitters
•  Ecstasy = artificial stimulation of dopamine and
serotonin neurons to a higher degree than
normal
•  This over-stimulation can selectively kill the
neurons that normally release dopamine &
serotonin
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Neurodegenerative Effects
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Level of
dysfunction
Neurodegenerative Effects
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Level of
dysfunction
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Drugs & Mechanisms of Action 33
DRUG:
Behavioral:
Mechanism:
Amphetamine
Excitement,
elevated mood
Increased release of dopamine
Cocaine
Excitement,
elevated mood
Blocks dopamine reuptake
Methylphenidate
(Ritalin)
Increased
concentration
Blocks dopamine reuptake
gradually
Nicotine
Stimulant
effects,
tremors
Activates acetylocholine (ACh)
receptor (neuromuscular
synapses), increases dopamine
in nucleus of accumbens
Alcohol
Relaxation,
intoxication
Inhibits Na flux, activates GABA,
inhibits dopamine
Opiates
Relaxation,
decrease pain
Stimulates endorphin receptors
Drugs & Mechanisms of Action 34
DRUG:
Behavioral:
Mechanism:
Phencyclidine
(PCP)
Intoxication,
hallucinations
thought /
memory
disorders
Inhibits NMDA-type glutamate
receptors (found in specific areas
in the temporal and occipital
lobes)
Marijuana
Intensified
Activates anandamide receptors
sensory,
(hippocampus, basal ganglion,
reduced pain,
cerebellum)
inhibit learning
LSD
Distorted
sensations
Stimulates serotonin receptors
Caffeine
Increased
arousal
Vasoconstrictor, blocks
adenosine (effectively increasing
dopamine & ACh)
MDMA (ecstasy)
Euphoria,
hallucinations
Stimulates release of dopamine,
activates serotonin receptors
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For next time…
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•  Read Ch. 5
•  Study for Exam 1
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