Download Receptors

Specific Neurotransmitter Systems
(& drugs that affect them)
• Acetylcholine
• Monoamines
– Dopamine
– Noradrenaline & Adrenaline
– Serotonin
• Amino Acids
– Glutamate
– GABA
•
Opioids
•
•
THC
Adenosine (caffeine)
Receptors for Acetylcholine
Cholinergic neurons
(release Acetylcholine)
Nicotine: Stimulates
Nicotinic receptors
- Muscarinic
- Nicotinic
Curare: Blocks nicotinic receptors
1. produce
2. pack
3. release
4. Bind
5. Post-synaptic changes
BOTOX
Ach-E
Atropine: Blocks muscarinic receptors
6.B Destroy
Pre-synaptic
Neuron
(axon)
Alzheimer’s treatment
Inhibits Ach-E
Post-synaptic
neuron
(dendrite)
Belladonna
(atropine)
curare
Acetylcholine (Ach)
• Important for:
–
–
–
–
–
Muscle
Botox prevents release by terminal buttons (Antagonist)
Vigilance Nicotine mimics Ach effect in brain (Agonist)
Memory
Anti-cholinesterase drugs for Alzheimer’s disease (Agonist)
Learning Anticholinergic drugs (to prevent vomit) (Antagonist)
Autonomic Nervous System
• Cholinergic neurons (release Ach)
• Receptors:
– Nicotinic (ionotropic):
stimulated by nicotine, blocked by curare
– Muscarinic (metabotropic): blocked by atropine (belladona)
Dopaminergic neurons
Receptors for dopamine
- D1, D2, D4
(release dopamine)
MAO
inhibitor
L-Dopa
Inactive substance
Mono-amino
Oxidase (MAO)
D2
Antipsychotic drugs for schizophrenia
Blocks D2 receptors
Precursor dopamine
pack
D2
release
Bind
Recycle
Pre-synaptic
Neuron
(axon)
Cocaine, amphetamine,
Methylphenidate (ritalin)
Makes dopamine transporter
work in reverse
Post-synaptic changes
D1
Post-synaptic
neuron
(dendrite)
Dopamine (DA)
• Important in:
– Movement control
– Drug addiction
– Schizophrenia (?)
– ADHD
death of dopaminergic cells in Parkinson’s disease
amphetamine, cocaine (agonist)
anti-psychotic drugs (antagonists)
metylphenidate (ritalin)
• dopaminergic neurons (release DA)
– Substantia nigra:
– Ventral Tegmental Area (VTA):
– VTA to frontal cortex
•
•
movement control
drug addiction
schizophrenia (?)
Receptors: D1, D2, D4
Group Activity:
– Would PD treatment with L-dopa increase or decrease hallucinations? (one of the
symptoms of schizophrenia)
– Would antipsychotic drugs produce PD like symptoms as a side effect (e.g., motor
problems)? Why? Why not?
– Schizophrenic patients often fail to take their medication, despite the benefitial effects.
Can you provide a physiological explanation? (hint: which systems does the drug
block?)
Noradrenaline & Adrenaline
• Aka: norepinephrine &
epinephrine
• Important for:
– Vigilance (adrenaline
response)
• Noradrenaline acts as a
neurotransmitter
• Adrenaline acts also as a
hormone
• Receptors:
– Alpha
– Beta: beta-blockers are
used for hypertension
Oh no!
my
sympathetic
nervous
system is
overactive
again!
Serotonin (5-HT)
• Important in:
– Depression
• Receptors:
– Way too many!
• Drugs:
– Fluoxetine (prozac): inhibitor of reuptake (recycle) (SSRI)
– LSD: agonist of 5-HT2A
– Ectasy: agonist for serotonin and agonist for noradrenaline
Glutamate
• Is the most pervasive excitatory NT in the brain
• Receptors:
– Four types (remember NMDA):
• Important in:
– Learning (NMDA receptor in the hippocampus)
• Drugs:
– Alcohol: NMDA antagonist
• Sleepy, impaired cognitive performance
• Alcohol withdrawal  seizures
GABA
• Is the most pervasive inhibitory NT in the brain
• Receptors:
– GABAa: opens Cl- channel
– GABAb: opens K+
– Question: does it puzzle you that, being GABA an inhibitory NT, GABAa
and GABAb receptors open channels of different polarity? Justify
• Drugs:
– Benzodiazepines (valium): GABA Agonist
• For reducing anxiety, promoting sleep, anti-convulsant, muscle
relaxant
– Alcohol: GABA agonist
• Anxiolytic
• Don’t drink while taking this medication
• Alcohol withdrawal  seizures
Opioids
• There are endogenous opioids (NT released by the brain)
• There are exogenous opioids (heroin, morphine, percodan)
• Drug Effects:
– Analgesia (morphine)
– Activates Reward system (addictive power)
– Inhibits defensive response (e.g., hiding)
•
Antagonist:
– Naloxone:
• Use in the acute treatment of heroin overdose
• Blocks analgesic effect of placebo
Cannabinoids (THC)
• There are endogenous & exogenous cannabinoids (marijuana)
• They are lipids:
– They mix well in butter (cookies) & oil (pesto), but not in alcohol or water.
– They depot in fat tissue: thus metabolites can be detected in urine long
after the psychoactive effect
• Drug Effects:
– Analgesia
– Sedation
– Stimulates eating (munchies)
– Reduces concentration & memory
– Distorts time perception
•
Antagonist (Naloxone): THIS BELONGS IN OPIATE SLIDE
• Use in the acute treatment of heroin overdose
• Blocks analgesic effect of placebo
Alcohol
• Alcohol acts on many systems:
– Blocks NMDA: that is why memory is impaired, and
why alcohol withdrawal can trigger seizures
– GABA: That is why at low levels alcohol has an
anxiolytic effect
– Dopamine (mesolimbic system): increases release
of DA in nucleus accumbens, thus the euphoria,
addictive power of alcohol