definiens: 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 monoalnines, serotonin ( 5 - HT ) and norepinephrine ( NA ) . The sole mode of action means a low binding affinity ( > I OOOnM ) on standard assays for dopamine D 1-"and D2 dass receptors ; serotonergic I, 2, and 3 class reeeptors ; adrenergic alpha 400543 vl21SD 8J2712!.DOC 10 . * Confidential Treatment Requested and beta receptors ; cholinergic nicotinic and muscanmc receptors ; glutamatergic AMP A, Kainate, NMDA, and metabotropic receptors ; histaminegic 1 - and 2 - C\ass ' receptors ; MU-, kappa-, delta - opioid receptors ; Orphanin ( ORLl ) receptors ; Neurokinin ( NKI, NK2, NK3 ) receptors ; Neuropeptide Yreceptors ; Sigma ( sigma - I, sigma-2 ) receptors ; Vanilloid receptors ;, Adenosine A I receptors ; Calcitonin gene - related peptide ( CGRP ) receptor ; Cannabinoid ( CB I, CB2 ) receptors ; Cholecystokinin ( CCKI, CCK2 ) receptors ; Nerotensin receptors ; Voltage - gated calcium channels ( N-, P / Q-, L-, T - type ) ; Voltage - gated sodium channels ; Bradykinin ( Bl, B2 ) receptors ; GABA - A, GABA - B receptors ; Galanin ( GALl, GAL2)receptors ; Neuropeptide FF receptors ; Melanocortin ( MCI, MC3, MC4, MC5 ) receptors ; Prostanoid ( EPl ) receptors ; Endothelin ( ETA, ETB ) receptors ; and Prostanoid ( TXA2 ) receptors . The agent should also not effect MAO - A and ~B enzyme activity . The IC50 or KI of in vitro reuptake inhibition for NA and 5 - HT must be both < lOOOnM, while the selectivity ratio for 5 - HT and NA ( Le ., IC50 or KI of 5 : HT in vitro reuptake inhibition divided by that of NA ) must range between 0.2 and 5