Chemistry of Anxiolytics

Question 1

What are the neurotransmitters associated with anxiety

Answer 1

GABA, norepinephrine, serotonin

Question 2

What are the steroids in the brain connected to anxiety, what do they do

Answer 2

Allopregnanolone, AllotetrahydroDOC, Androstanediol/ GABA receptor activation

Question 3

What is the structure of a steroid

Answer 3

17 carbon moeity with 3 cyclohexane rings and one cyclopentane ring

Question 4

What are the enzymes that create neurosteroids, how

Answer 4

5- alpha reductase and 3-alph hydroxysteroid dehydrogenase, reduce enone

Question 5

What do neurosteroids do in the bain

Answer 5

barbiturate-like modulators of GABA receptors, positive modulators of GABA receptor (indirect effect)

Question 6

What group of antiaxiolytics works on the serotonin receptor (5-HT1A), most associated with anxiety

Answer 6

Azapirones, buspirone

Question 7

T/F: Azapirones have no tolerance or withdrawl side effects

Answer 7

True

Question 8

What is the important part of azapirones are responsible for receptor binding, selectivity

Answer 8

Pyrimidin-piperazine (5.2 to 5.6 angstroms in length), azaspiro-decandione

Question 9

What is the MOA of buspirone at low doses (30 mg), high doses (greater than 60 mg)

Answer 9

agonist at pre-synaptic 5HT1A receptors causing a REDUCTION in 5-HT relase from the pre-synaptic terminal, partial 5-HT1A agonist at post-synaptic receptors for the antidepressant properties

Question 10

Why does buspirone also have alpha-2-adrenoceptor antagonist activity

Answer 10

1-(2-pyrimidyl)-piperazine or 1-PP is the major hepatic metabolite and it is less selective

Question 11

What are allosteric sites on the GABA receptor

Answer 11

Benzodiapine, barbiturate, ethanol, neuroactive steroids

Question 12

What ion is most commonly associated with the GABA receptor, what are the most common peptide units

Answer 12

Chloride/ two alpha-subunits, two beta subunits, most commonly one gamma subunit (needed for BZD binding)

Question 13

What happens when GABA binds to the GABA receptor

Answer 13

Conformation change opens the chloride ion channel causing neuronal membrane hyperpolarization (inhibition)

Question 14

Where do BZDs bind to, what effect does this have on GABA receptor

Answer 14

interface of the gamma-2 subunit and the respective alpha-subunit, Increased FREQUENCY of chloride channel opening

Question 15

T/F: BZDs binding at the alpha-1 subunit causes antiolysis

Answer 15

False: BZDs binding at the alpha-2 subunit causes anxiolysis, alpha-1 causes sedation, anticonvulsant, and anterograde amnesia

Question 16

T/F: Barbituates also increase the frequency of the chloride channels opening and thus can be used for anxiety

Answer 16

False: Barbiutates increased the duration of chloride channel opening and cause sedation and have no effect in anxiety (GABA independent)

Question 17

How does ethanol interact with the GABA receptor

Answer 17

Binds to a distinct site on the ionophore and enhances chloride influx

Question 18

T/F: Lidocaine can causes anxiety due to being metabolized into an inverse agonist that binds in the BZD binding spot

Answer 18

True

Question 19

What is the structure for benzodiapeines

Answer 19

fusion of a benezene ring and diazepine

Question 20

Which BZD needs to be converted in acidic conditions for bioactivation, what should be avioded

Answer 20

Chlorazepate (long acting), antacids

Question 21

What is the BZD antagonist, when is it used

Answer 21

Flumazenil (competitive), overdose

Question 22

What are the partial agonists that bind the BZD receptor

Answer 22

Bretazenil and Abecarnil