SNRI product

SNRI product. Shall mean any serotonin norepinephrine reuptake inhibitor product, meaning an agent whose sole mode of action (including major metabolites) is through the selective reuptake inhibition of the two monoamines, serotonin (5-HT) and norepinephrine (NA). The sole mode of action means a low binding affinity (1000nM) on standard assays for dopamine D1- and D2 class; serotonergic 1, 2, and 3 class; adrenergic alpha and beta; cholinergic nicotinic and muscarinic; glutamatergic AMPA, Kainate, NMDA, and...d metabotropic; and histaminegic 1- and 2-class receptors. The agent should also not effect MAO-A and –B enzyme activity. The IC50 or KI of in vivo reuptake inhibition for NA and 5-HT must be both <1000nM, while the selectivity ratio for 5-HT and NA (i.e., IC50 or KI of 5-HT in vivo reuptake inhibition divided by that of NA) must range between 0.2 and 5. Similarly, the IC50 of KI of in vivo reuptake inhibition for dopamine must be >1000 nM, with a selectivity ratio for dopamine vs. NA or 5-HT of >50. Finally, the agent must not effect the release of the amines, including 5-HT, NA and dopamine. View More