Neurotransmission and Drugs Flashcards
What happens when a neurotransmitter binds to a receptor?
The receptor becomes activated like a key and lock
Ligand
a molecule that binds to a receptor
What happens to neurotransmitters leftover in the synaptic cleft
They get destroyed by enzymes or reuptake ( reabsorption of neurotransmitter by presynaptic neurons
How many NT are there
Dozens- 5-10 major types
How are NT generalized
And what determines the effect
By anatomical localization By effect (EPSP or IPSP) The postsynaptic receptors and channels
The most common NT found in the nervous system, found throughout the brain
Excitatory (induces EPSPs)
Glutamate
Glutamate receptors induce depolarization following NT binding
Participates in numerous processes, emphasis on learning and memory
What are the 3 types of receptors for glutamate
- AMPA (ionotropic)
- NMDA (ionotropic)
- mGluR (metabotropic)
GABA
Gamma Amino Butyric Acid Most common inhibitory NT Causes IPSPs Found throughout the brain Opens either chloride channels (Cl- into cell) or potassium channels (K+ ions out of the cell)
2 receptors for GABA
- GABAA
2. GABAB
ACh
Acetylcholine
Usually EPSPs
In brain and PNS
What does ACh affect in the brain
Sensation, learning, and action
What does ACh affect in the PNS
Peripheral motor neurons
Parasympathetic system
Neuromuscular junction
A synapse between a motor neuron and a muscle fiber
What NT is at the neuromuscular junction
ACh
Sarin
Extremely toxic chemical weapon
Inhibitor of acetylcholinesterase ( an ACh degrader)
Causes ACh buildup, prevents muscle relaxation
The family of Catecholamines
Adrenaline
Noradrenaline
Dopamine
Both EPSP & IPSP
Norepinephrine
aka Noradrenaline
General function is to mobilize the brain and body for action
Sympathetic autonomic system
Produced in small structures, widespread affect
Most notably in the Locus Coeruleus
Dopamine
Movement, reward, motivation
Produced in the Substantia Nigra and Ventral Tegmental Area
How many families of dopamine receptors are there
2
D1 & D2
Serotonin (5-HT)
Known as "happiness NT" Sleep, appetite Antidepressant drugs increase serotonin Produced in the Raphe Nuclei Mixed EPSPs & IPSPs
Opioids
Endorphin and Enkephalin "Natural morphine" Pain reduction, reward, euphoria Mixed EPSPs & IPSPs Bind to opioid receptors Synthesized following pain, exercise and laughter
Nitric Oxide
Reverse NT
Soluble gas in dendrites-generated by postsynaptic enzyme in response to NT
Leaks out of dendrite
Enters presynaptic neuron-needs no membrane receptor. Penetrates inside neuron directly
Activates presynaptic secondary messenger
Feedback
How many receptor subtypes are there for acetylcholine
2 or more (ionotropic and metabotropic)
How many receptor subtypes are there for dopamine
5 or more (metabotropic)
In 2 families (D1 vs D2)
How many receptor subtypes are there for norepinephrine
4 or more (metabotropic)
How many receptor subtypes are there for serotonin
7 or more (ionotropic and metabotropic)
How many receptor subtypes are there for glutamate
5 or more (ionotropic and metabotropic)
How many receptor subtypes are there for GABA
10 or more (ionotropic and metabotropic)
How many receptor subtypes are there for opioids
3 or more (metabotropic)
What do most psychoactive drugs act on
synapses
Agonists-
Presynaptic:
Postsynaptic:
Turn ON NT system (EPSP or IPSP)
Release NT
Activate receptors
Antagonists-
Presynaptic:
Postsynaptic:
Turn OFF NT system
Prevent release
Block receptors
Inverse agonists
Postsynaptic bind to receptors but induces opposite effect
Parkinsons disease
Reduced dopamine levels
Medication: L-Dopa
L-Dopa is a dopamine precursor
Presynaptic agonists
Cocaine
Presynaptic agonist
Inhibits reuptake of dopamine by blocking dopamine transporter. Also blocks serotonin and norepinephrine
Amphetamine
Blocks and reverses dopamine transporter
Increases levels of dopamine and norepinephrine
Stimulation, euphoria, wakefulness, improved cognitive control
Used in treatment of ADHD, narcolepsy, depression; athletic performance enhancer
Adderall
Prescribed combination of amphetamine and dextroamphetamine
Ritaline
Not amphetamine, but similar effect
Selective Serotonin Reuptake Inhibitors
SSRIs
Block reuptake of Serotonin
Commonly prescribed antidepressant: Prozac
Morphine and Heroin
Postsynaptic Agonists
Activate postsynaptic opioid receptors
Euphoric, pain relief
Mimic endorphins, enkephalin
Synthetic Opioid Drugs
Fentanil- 50X more potent than heroin
Carfentanil- 100X more potent than fentanil
Pain reduction, tranquilizer darts
Overdose inhibits brainstem breathing circuits
LSD (Lysergic Acid Diethylamide)
Postsynaptic agonist
Hallucinogenic Drug
Activates serotonin receptors
Benzodiazepines
Xanax, Valium
Postsynaptic agonist
Sedative, hypnotic, anxiolytic (anti-anxiety), anti-epileptic, muscle relaxant
Bind to GABA receptors and facilitate GABA effects
Antipsychotic Drugs for Schizophrenia
Pimozide, haloperidol
Block D2 dopamine receptors
Prevent dopamine from activating
Atypical Antipsychotics
Block serotonin receptors
Still block dopamine too
Routes of administration of drugs
Oral
Sniff and nasal mucosa
Intravenous injection
Smoke
Long-term effects
1. Receptor-Down Regulation
Tolerance to drug
-Fewer receptors to activate
Withdrawal in absence
-Normal NT gives lower signal
Long-term effects
2. Neural Sensitization
Hyper responsive to drug
Dopamine sensitization and addiction
-Wanting vs. liking
Long-term effects
3. Neurotoxicity
Amphetamine
Kills dopamine neurons
Toxic at 10X street dose
