How Drugs Control The Brain

Question 1

What is an example of GABAergic projection neuron?

Answer 1

Cerebellar purkinje cells

Question 2

Difference between GABA A and B?

Answer 2

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

Question 3

GABA A receptor structure?

Answer 3

Heteropentameric- 2 alpha 2 bets and 1 gamma

Cl- channel gated by binding of 2 agonist molecules

Question 4

GABA A antagonist?

Answer 4

Picrotoxin- convulsions

Question 5

What can bind at GABBa A receptors?

Answer 5

Barbiturates and steroids

Question 6

What is a direct agonist ad antagonist of GABA?

Answer 6

Agonist- muscimol

Antagonist- bicuculine

Question 7

What are indirect agonists of GABA A?

Answer 7

Benzodiazepines- binding increases the receptor affinity for GABA, frequency of channel opening
Anxiolytics and hypnotic drugs

Barbiturates- increase the duration of channels

Alcohol

Question 8

Where does benzodiazepine bind?

Answer 8

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

Question 9

Combining which 2 is fatal?

Answer 9

Barbiturates and alcohol

Question 10

Effect of alcohol on GABA A?

Answer 10

Low- mild euphoria and anxiolytics effects

High dose- incoordination amnesia

Question 11

Agonist for GABA B?

Answer 11

Baclofen (muscle relaxant to reduce spasticity in Huntington’s)

Question 12

Dopaminergic system contains?

Answer 12

Nigrostriatal system- 75% of brain

Mesolithic
Mesocortical
Tuberohypophyseal

Question 13

D1 family 1 and 5 have which G protein?

Answer 13

Gs- stimulates adenylyl cyclase and phospholipase C postsynaptic

Question 14

D2 family causes?

Answer 14

Gi- inhibits adenylyl cyclase, opens K channels and closes ca channels
Postsynaptic and presynaptic autoreceptors

Question 15

Nigrostriatal system starts and ends where?

Answer 15

Cell bodies in substantia nigra project to striatum caudate nucleus and putamen

Question 16

Drugs for nigrostriatal system?

Answer 16

L DOPA, MAO, dopamine receptor agonist

Question 17

Where does Mesolimbic system begin and end?

Answer 17

Begins ventral tegmental area and ends at nucleus accumbens

Question 18

Mesolimbic drugs?

Answer 18

Cocaine amphetamine

Question 19

Mesocortical system begins where?

Answer 19

VTA to prefrontal cortex, role in working memory

Question 20

Drugs for mesocortical system?

Answer 20

Typical antipsychotics
Chlorpromazine and haloperidol extrapyramidal side effects- tar dive dyskinesia

Atypical antipsychotic e.g clozapine antagonist of D4 only

Reduce psychosis

Question 21

With SSRIs what is needed?

Answer 21

Need to wait 2/3 weeks, gene transcription, second messenger cascades, long term modulatory effects

Question 22

Drugs for seretonergic system?

Answer 22

MDMA- make seretonin and NE transporters run in reverse

Fluoxetine

Question 23

What is LSD and where does it bind?

Answer 23

Hallucinogen, binds at 5HT1A receptor in raphe nucleus

And hallucinogenic properties at 5HT2A receptors in prefrontal cortex

Question 24

Where does noradrenergic system begin?

Answer 24

Locus coeruleus Metabotropic receptors

Alpha adrenergic receptors
a1 Gq
a2 Gi

Beta adrenergic receptors
b1, 2 and 3 Gs

Question 25

Where does adrenergic system begin and end?

Answer 25

Lateral tegmental area to thalamus and hypothalamus

Question 26

Where is the cholinergic system?

Answer 26

Basal forebrain complex- cholinergic innervation of hippocampus and neocortex

Brain stem complex- innervates dorsal thalamus and telencephalon

Question 27

Cholinergic disorders?

Answer 27

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

Question 28

Treatment of Alzheimer’s drug?

Answer 28

Physostigmine

Question 29

Treatment of myasthenia gravis?

Answer 29

Neostigmine

Question 30

Chemical warfare agents?

Answer 30

Sarin

Question 31

How does latrotoxin work?

Answer 31

Causes permanent release at NMJ

Question 32

What is a Ach metabotropic antagonist?

Answer 32

atropine

Question 33

M1 3 and 5?

Answer 33

via Gq to phospatidylinositol hydrolysis

Question 34

M2 and 4?

Answer 34

via Gi to inhibit cAMP

Question 35

Nicotinic receptors?

Answer 35

Muscle receptor 2x a1, b, d and g subunits

Question 36

Nictonic anatgonist?

Answer 36

Curare

Question 37

Histaminergic receptors?

Answer 37

3 G-protein-coupled Rs

Question 38

Role of histaminergic system?

Answer 38

Arousal & attention
Reactivity of vestibular system
Mediation of allergic responses
Influence of brain blood flow