Dopaminergic

Question 1

D1/D5 family are located where and are coupled with what G-protein?

Answer 1

Postsynaptic, Gs activation of adenylate cyclase, cAMP increase.

Question 2

D2/D3/D4 are located where and are coupled with what G-protein?

Answer 2

Pre and post synaptic. Gi, inhibit adenylate cyclase, decrease cAMP

Question 3

What is the alpha rotamer, and what selectivity does it have?

Answer 3

Meta hydroxy group and basic nitrogen group are on the same side. Non-selective D agonist.

Question 4

What is the beta rotamer and what is the selectivity?

Answer 4

Meta hydroxy group and basic nitrogen group are on opposite sides. D2 agonist > D1 agonist selectivity.

Question 5

How is dopamine activity terminated, which is primary mechanism?

Answer 5

Primarily by reuptake by active transporter located on presynaptic. Second by metabolism by MAO or COMT.

Question 6

What does dopamine control in the basal ganglia?

Answer 6

Particularly in the nigrostriatal pathway, posture, muscle tone, movement coordination. Lack of DA cause EPS.

Question 7

What does dopamine do in the mesolimbic system?

Answer 7

Control behavior and emotion

Question 8

What does dopamine do in the tuberoinfunibular system?

Answer 8

Decreases prolactin release.

Question 9

What does dopamine do in the mesoaccumbens pathway?

Answer 9

Controls locomotor functions.

Question 10

What drus affect the biosynthesis of dopoamine?

Answer 10

A-methyltyrosine = inhibits tyrosine hydroxylase
Carbidopa= inhibits LAAAD by reacting to pyridoxal

Question 11

What drug affects the storage of dopamine?

Answer 11

Amantadine( looks like a cube)

It increases dopamine release, decreases reuptake.

Question 12

What drugs affect the release of dopamine?

Answer 12

Y-butyrolactone(OH——–carboxylic acid)

Mimics GABA, decreases dopamine release.

Question 13

Describe the non-selective agonists.

Answer 13

Mimic alpha rotamer(same side basic nitrogen and meta hydroxy)
4 cyclic, with 1 catechol
Br to 4 cyclic linked by amide to 3 cyclic

Question 14

Describe the D2 selective agonists

Answer 14

Mimic the beta rotamer(meta hydroxy and basic nitrogen opposite sides)
Frog and 1-legged frog

Question 15

What are the uses for dopamine agonists?

Answer 15

Parkinson’s disease

Question 16

What are the uses for dopamine antagonists?

Answer 16

Antipsychotics , depression, bipolar disorder

Question 17

Describe the phenothiazine system.

Answer 17

C-1, C-4 needs to be empty
C-2 EWG required for activity.
N-10 unbranched, otherwise decrease potency

Question 18

Which would be best and worst for activity.

Thioether, sulfonium, quartnary amine, 3 amine.

Answer 18

Best 3 amine, 4 amine, sulfonium, thioether worst

Question 19

Which conformation is better with the phenothiazines?

Answer 19

CIS is better than trans for binding.

Question 20

Which antipsychotics are most potent, least potent?

Answer 20

Piperazines most, piperidine, dialkylamino

Question 21

Which antipsychotics cause the most EPS?

Answer 21

Piperazines most, dialkylamino, piperidine least

Question 22

Which antipsychotcs cause the most sedation?

Answer 22

Dialkylamino = pipieridines, piperazines

Question 23

Which antipsychotics cause the most hypotensive effects?

Answer 23

Dialkylamino ~ piperidines, piperazines

Question 24

What are the characterisitics of a typical antipsychotic?

Answer 24

Potent D2 antagonist
High EPS
No 5-HT2 antagonism

Question 25

Describe the thioxanthene.

Answer 25

Tricyclic sulfur containing. sulfone in EWG Double bond will abolish the free rotation and lock it into CIS D2 antagonist

Question 26

Describe the dibenzooxazepines.

Answer 26

Tricyclic containing oxygen. Cl EWG Locked into CIS conformation, no free rotation. D2 antagonist

Question 27

Describe the fluorobutyrophenones.

Answer 27

Fluorophenyl, 4 carbon chain, attaches to nitrogen of the piperidine. D2 antagonists, high EPS

Question 28

What are the characteristics of the atypical agents?

Answer 28

Lower affinity for D2 receptors Lower EPS Second generation 5-HT2 antagonism

Question 29

Describe the diphenylbutylpiperidine.

Answer 29

D2 antagonist atypical, with lower EPS than typical antipsychotics. Two Fluorophenyl

Question 30

Describe the benzoisoxazoles, benzoisothiazole.

Answer 30

D2 antagonist and 5-HT2 antagonist. | Very low EPS.

Question 31

Describe the dibenzodiazepines.

Answer 31

Atypical antipsychotics, low affinity for D2 receptors. A1-antagonists, anticholinergic, antihistaminergic. Selective for D2 in limbic versus basal ganglia.

Question 32

Which drug has selectivity for D4 receptors?

Answer 32

Clozapine. Cl EWG opposite from the basic nitrogen. Trans conformation. Can cause agranulocytosis.

Question 33

Describe the COMT inhibitors.

Answer 33

Catechol with nitro group. Disrupts the metabolism of dopamine.

Question 34

Describe the MAO inhibitors.

Answer 34

Irreversible, increases dopamine, by decreases the metabolism. Contain a triple C bond.

Question 35

Where does parkinson's disease occur and what are the symptoms?

Answer 35

In nigrostriatal. | Symptoms: muscle tremor, rigidity, bradykinesia

Question 36

What drugs are used for parkinson's?

Answer 36

Dopamine agonists, MAO-B inhibitors, anticholinergics, COMT inhibitor, amantidine, L-dopa, carbidopa

Question 37

What are the symptoms of schizophrenia and what drugs are used to treat it?

Answer 37

Positive= delusions, hallucination, behavior, disorganize speech Negative=flattened affect, social withdrawal Antipsychotics , lack euphoric effect, less sedation, less tolerance, less respiratory depression.

Question 38

Antagonism of the dopamine receptors in the basal ganglia results in?

Answer 38

EPS

Question 39

Antagonism of dopamine receptors in the tuberoinfundibular results in?

Answer 39

Increase release of prolactin

Question 40

Antagonist of D2 presynaptic receptors cause what initially, then what over time?

Answer 40

Initially increase in dopamine release. | Depolarization inactivation with decrease release and biosynthesis of dopamine.

Question 41

What drug classes are typical antipsychotics?

Answer 41

Phenothiazines Thioxanthenes Fluorobutyrophenones

Question 42

What drug classes are atypical antipsychotics?

Answer 42

Diphenylbutylpiperidine Benzoisoxazole Benzoisothiazole Dibenzodiazepines

Question 43

Describe the long chain arylpiperazine.

Answer 43

High affibity for D2/D3, serotonin 5-HT1/5-HT2a Partial agonist at D2, 5-HT1a Antagonist at 5-HT2a Orthostatic hypotension antagonist at alpha1