Neuropharmacology

Question 1

tetrabenazine (Xenazine)
valbenazine (Ingrezza)
deutetrabenazine (Austedo)

Answer 1

vesicular monoamine transporter 2 inhibitors (decreasing uptake into synaptic vesicles, making less monoamine available for release into synapse); also necessary for GABA release in nigrostriatal and mesolimibic DA neurons; type 2 is found in CNS; used as treatment for tardive dyskinesia. Watch for depression.

VMAT-2 has 2 minding sites: one binds TBZ (and amphetamine) and the other reserpine (and meth).

Question 2

varenicline (Chantix)

Answer 2

alpha-4-beta-2 nicotinic acetylcholine receptor partial agonist (leads to less DA release than full agonist, nicotine)

a4b2 nicotinic receptors bind 90% of nicotine in CNS. Found diffusely in brain, but greatest in thalamus.

Question 3

levomilnaciprin (Fetzima)

Answer 3

N-SRI - more effect of norepinephrine and therefore should produce more benefit for concentration and motivation leading to improved social function. Its parent compound, milnaciprin, is approved only for treating fibromyalgia pain. This compound has NOT been approved for treating pain, but could theoretically have benefit. Can raise heart rate and BP, cause urinary hesitancy and ED. Approved only for treating functional impairment in depression. 3A4, adjust dose with moderate renal impairment.

Question 4

vilazodone (Vybriid)

Answer 4

5HT transporter inhibitor (also some DAT and NET inhibition), partial agonist at 5HT1A receptor (like Buspar, initially inhibits serotonin synthesis and neuronal firing), binds 5HT4 receptor (mostly found in gut). Approved for depression, can theoretically benefit anxiety and gut problems (IBS). Take with food (73% available with food). 3A4 substrate - reduce to 20mg if given with 3A4 inhibitor (ie - Tegretol) SE: headache, GI symptoms. No reported sexual SE.

Question 5

vortioxetine (Trintellix)

Answer 5

5HT transported inhibitor, as well as an inhibitor at 5HT1D and 5HT7 receptors. It is an agonist at 5HT1A receptors, a partial agonist at 5HT1B receptors and an antagonist at 5HT3 receptors. It has downstream effects of increasing NE, DA and ACh in the PFC, which are thought to aid in improving the cognitive effects of depression. It is the only antidepressant specifically studied for its effects on cognitive deficits. It has been studied in geriatric populations. Half-life of 66 hours. 2D6 substrate - Wellbutrin increases its blood level by 128%.