Chemistry of Anxiolytics Flashcards
What are the neurotransmitters associated with anxiety
GABA, norepinephrine, serotonin
What are the steroids in the brain connected to anxiety, what do they do
Allopregnanolone, AllotetrahydroDOC, Androstanediol/ GABA receptor activation
What is the structure of a steroid
17 carbon moeity with 3 cyclohexane rings and one cyclopentane ring
What are the enzymes that create neurosteroids, how
5- alpha reductase and 3-alph hydroxysteroid dehydrogenase, reduce enone
What do neurosteroids do in the bain
barbiturate-like modulators of GABA receptors, positive modulators of GABA receptor (indirect effect)
What group of antiaxiolytics works on the serotonin receptor (5-HT1A), most associated with anxiety
Azapirones, buspirone
T/F: Azapirones have no tolerance or withdrawl side effects
True
What is the important part of azapirones are responsible for receptor binding, selectivity
Pyrimidin-piperazine (5.2 to 5.6 angstroms in length), azaspiro-decandione
What is the MOA of buspirone at low doses (30 mg), high doses (greater than 60 mg)
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
Why does buspirone also have alpha-2-adrenoceptor antagonist activity
1-(2-pyrimidyl)-piperazine or 1-PP is the major hepatic metabolite and it is less selective
What are allosteric sites on the GABA receptor
Benzodiapine, barbiturate, ethanol, neuroactive steroids
What ion is most commonly associated with the GABA receptor, what are the most common peptide units
Chloride/ two alpha-subunits, two beta subunits, most commonly one gamma subunit (needed for BZD binding)
What happens when GABA binds to the GABA receptor
Conformation change opens the chloride ion channel causing neuronal membrane hyperpolarization (inhibition)
Where do BZDs bind to, what effect does this have on GABA receptor
interface of the gamma-2 subunit and the respective alpha-subunit, Increased FREQUENCY of chloride channel opening
T/F: BZDs binding at the alpha-1 subunit causes antiolysis
False: BZDs binding at the alpha-2 subunit causes anxiolysis, alpha-1 causes sedation, anticonvulsant, and anterograde amnesia
T/F: Barbituates also increase the frequency of the chloride channels opening and thus can be used for anxiety
False: Barbiutates increased the duration of chloride channel opening and cause sedation and have no effect in anxiety (GABA independent)
How does ethanol interact with the GABA receptor
Binds to a distinct site on the ionophore and enhances chloride influx
T/F: Lidocaine can causes anxiety due to being metabolized into an inverse agonist that binds in the BZD binding spot
True
What is the structure for benzodiapeines
fusion of a benezene ring and diazepine
Which BZD needs to be converted in acidic conditions for bioactivation, what should be avioded
Chlorazepate (long acting), antacids
What is the BZD antagonist, when is it used
Flumazenil (competitive), overdose
What are the partial agonists that bind the BZD receptor
Bretazenil and Abecarnil
