How Drugs Control The Brain Flashcards
What is an example of GABAergic projection neuron?
Cerebellar purkinje cells
Difference between GABA A and B?
A- ionotropic
Ligand gated Cl- channel
Fast IPSPs
Mainly GABAergic interneurons
B- metabotropic G protein coupled receptor Indirectly couples to K or ca channel through second messenger SLow IPSPs Both presynaptic and postynaptic
GABA A receptor structure?
Heteropentameric- 2 alpha 2 bets and 1 gamma
Cl- channel gated by binding of 2 agonist molecules
GABA A antagonist?
Picrotoxin- convulsions
What can bind at GABBa A receptors?
Barbiturates and steroids
What is a direct agonist ad antagonist of GABA?
Agonist- muscimol
Antagonist- bicuculine
What are indirect agonists of GABA A?
Benzodiazepines- binding increases the receptor affinity for GABA, frequency of channel opening
Anxiolytics and hypnotic drugs
Barbiturates- increase the duration of channels
Alcohol
Where does benzodiazepine bind?
Alpha subunit on GABA A
Changes conformation of the receptor to make GABA activation more effective
Reduces anxiety
Cause sedation reduce convulsions
Relax muscle
Cause amnesia
Combining which 2 is fatal?
Barbiturates and alcohol
Effect of alcohol on GABA A?
Low- mild euphoria and anxiolytics effects
High dose- incoordination amnesia
Agonist for GABA B?
Baclofen (muscle relaxant to reduce spasticity in Huntington’s)
Dopaminergic system contains?
Nigrostriatal system- 75% of brain
Mesolithic
Mesocortical
Tuberohypophyseal
D1 family 1 and 5 have which G protein?
Gs- stimulates adenylyl cyclase and phospholipase C postsynaptic
D2 family causes?
Gi- inhibits adenylyl cyclase, opens K channels and closes ca channels
Postsynaptic and presynaptic autoreceptors
Nigrostriatal system starts and ends where?
Cell bodies in substantia nigra project to striatum caudate nucleus and putamen
Drugs for nigrostriatal system?
L DOPA, MAO, dopamine receptor agonist
Where does Mesolimbic system begin and end?
Begins ventral tegmental area and ends at nucleus accumbens
Mesolimbic drugs?
Cocaine amphetamine
Mesocortical system begins where?
VTA to prefrontal cortex, role in working memory
Drugs for mesocortical system?
Typical antipsychotics
Chlorpromazine and haloperidol extrapyramidal side effects- tar dive dyskinesia
Atypical antipsychotic e.g clozapine antagonist of D4 only
Reduce psychosis
With SSRIs what is needed?
Need to wait 2/3 weeks, gene transcription, second messenger cascades, long term modulatory effects
Drugs for seretonergic system?
MDMA- make seretonin and NE transporters run in reverse
Fluoxetine
What is LSD and where does it bind?
Hallucinogen, binds at 5HT1A receptor in raphe nucleus
And hallucinogenic properties at 5HT2A receptors in prefrontal cortex
Where does noradrenergic system begin?
Locus coeruleus Metabotropic receptors
Alpha adrenergic receptors
a1 Gq
a2 Gi
Beta adrenergic receptors
b1, 2 and 3 Gs
Where does adrenergic system begin and end?
Lateral tegmental area to thalamus and hypothalamus
Where is the cholinergic system?
Basal forebrain complex- cholinergic innervation of hippocampus and neocortex
Brain stem complex- innervates dorsal thalamus and telencephalon
Cholinergic disorders?
Peripheral myasthenia gravis- autoimmune disease destroys cholinergic receptor in muscle so muscle weakness
Brain- Alzheimer’s disease- loss of Ach neurons in basal ganglia
Addiction
Epilepsy- autosomal dominant nocturnal frontal lobe epilepsy
Treatment of Alzheimer’s drug?
Physostigmine
Treatment of myasthenia gravis?
Neostigmine
Chemical warfare agents?
Sarin
How does latrotoxin work?
Causes permanent release at NMJ
What is a Ach metabotropic antagonist?
atropine
M1 3 and 5?
via Gq to phospatidylinositol hydrolysis
M2 and 4?
via Gi to inhibit cAMP
Nicotinic receptors?
Muscle receptor 2x a1, b, d and g subunits
Nictonic anatgonist?
Curare
Histaminergic receptors?
3 G-protein-coupled Rs
Role of histaminergic system?
Arousal & attention
Reactivity of vestibular system
Mediation of allergic responses
Influence of brain blood flow
