Pharmacodynamics Dosulepin

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dosulepin transporter blocker of serotonin transporter (sert) , norepinephrine transporter (net), thereby acting snri. antagonist of histamine h1 receptor, α1-adrenergic receptor, serotonin 5-ht2 receptors, , muscarinic acetylcholine receptors (mach), blocker of voltage-gated sodium channels (vgscs). antidepressant effects of dosulepin thought due inhibition of reuptake of norepinephrine , possibly of serotonin.


dosulepin has 3 metabolites, northiaden (desmethyldosulepin), dosulepin sulfoxide, , northiaden sulfoxide, have longer terminal half-lives of dosulepin itself. however, whereas northiaden has potent activity dosulepin, 2 sulfoxide metabolites have dramatically reduced activity. have been described inactive, , considered unlikely contribute either therapeutic effects or side effects of dosulepin. relative dosulepin, northiaden has reduced activity serotonin reuptake inhibitor, antihistamine, , anticholinergic , greater potency norepinephrine reuptake inhibitor, other secondary amine tcas. unlike sulfoxide metabolites, northiaden thought play important role in effects of dosulepin.


although heal & cheetham (1992) reported relatively high ki values of 12 , 15 nm dosulepin , northiaden @ rat α2-adrenergic receptor , suggested antagonism of receptor involved in antidepressant effects of dosulepin, richelson & nelson (1984) found low kd of 2,400 nm dosulepin @ receptor using human brain tissue. suggests in fact has low potency action, other tcas.








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