Pharmacodynamics +<unk>  (and metabolite) Site Species Ref ' 8.6–78 192 Human/rat ' 46–70 25 Human/rat 5,310 2,539 Human/rat 5-HT1A 4,004 2,623 Rat 5-HT2A 152 141 Rat α1 419 950 Rat α2 2,400 Human H1 3.6–4 25 Human/rat ' 25–26 110 Human/rat M1 18 ' Human M2 109 ' Human M3 38 ' Human M4 61 ' Human M5 92 ' Human Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.<unk>  is a reuptake inhibitor of the serotonin transporter (SERT) and the norepinephrine transporter (NET), thereby acting as an SNRI. It is also an antagonist of the histamine H1 receptor, α1-adrenergic receptor, serotonin 5-HT2 receptors, and muscarinic acetylcholine receptors (mACh), as well as a blocker of voltage-gated sodium channels (VGSCs). The antidepressant effects of<unk>  are thought to be due to inhibition of the reuptake of norepinephrine and possibly also of serotonin.<unk>  has three metabolites, northiaden (desmethyldosulepin),<unk>  sulfoxide, and northiaden sulfoxide, which have longer terminal half-lives than that of<unk>  itself. However, whereas northiaden has potent activity similarly to<unk> , the two sulfoxide metabolites have dramatically reduced activity. They have been described as essentially inactive, and are considered unlikely to contribute to either the therapeutic effects or side effects of<unk> . Relative to<unk> , northiaden has reduced activity as a serotonin reuptake inhibitor, antihistamine, and anticholinergic and greater potency as a norepinephrine reuptake inhibitor, similarly to other secondary amine TCAs. Unlike the sulfoxide metabolites, northiaden is thought to play an important role in the effects of<unk> . Although Heal & Cheetham (1992) reported relatively high Ki values of 12 and 15 nM for<unk>  and northiaden at the rat α2-adrenergic receptor and suggested that antagonism of the receptor could be involved in the antidepressant effects of<unk> , Richelson & Nelson (1984) found a low KD of only 2,400 nM for<unk>  at this receptor using human brain tissue. This suggests that it in fact has low potency for this action, similarly to other TCAs. Pharmacokinetics<unk>  is readily absorbed from the small intestine and is extensively metabolized on first-pass through the liver into its chief active metabolite, northiaden. Peak plasma concentrations of between 30.4 and 279 ng/mL (103–944 nmol/L) occur within 2–3 hours of oral administration. It is distributed in breast milk and crosses the placenta and blood-brain barrier. It is highly bound to plasma proteins (84%), and has a whole-body elimination half-life of 51 hours.
Dosulepin
Pretomanid
Covaxin
Mucrocetin
Itruvone
Crotamiton
Celadrin 
Co-codaprin