antidepressant effects of dosulepin, Richelson & Nelson (1984) found a low KD of only 2,400 nM for dosulepin at this receptor using human brain tissue. This suggests that it in fact has low potency for this action, similarly to other TCAs. Pharmacokinetics Dosulepin 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. Chemistry Dosulepin is a tricyclic compound, specifically a dibenzothiepine, and possesses three rings fused together with a side chain attached in its chemical structure. It is the only TCA with a dibenzothiepine ring system to have been marketed. The drug is a tertiary amine TCA, with its side chain-demethylated metabolite northiaden (desmethyldosulepin) being a secondary amine. Other tertiary amine TCAs include amitriptyline, imipramine, clomipramine, doxepin, and trimipramine. Dosulepin exhibits (E) and (Z) stereoisomerism like doxepin but in contrast the pure E or trans isomer is used medicinally. The drug is used commercially as the hydrochloride salt; the free base is not used. History Dosulepin was developed by SPOFA. It was patented in 1962 and first appeared in the literature in 1962. The drug was first introduced for medical use in 1969, in the United Kingdom. Society and culture Generic names Dosulepin is the English and German generic name of the drug and its and , while dosulepin hydrochloride is its and . Dothiepin is the former of the drug while dothiepin hydrochloride is the former and remains the current . Its generic name in Spanish and Italian and its are dosulepina, in French and its are dosulépine, and in Latin is dosulepinum. Brand names Dosulepin is marketed throughout the world mainly under the brand name Prothiaden. It is or has been marketed under a variety of other brand names as well, including Altapin, Depresym, Dopress, Dothapax, Dothep, Idom, Prepadine, Protiaden, Protiadene, Thaden, and Xerenal. Availability Dosulepin is marketed throughout Europe (as Prothiaden, Protiaden, and Protiadene), Australia (as Dothep and Prothiaden), New Zealand (as Dopress) and South Africa (as Thaden). It is also available in Japan, Hong Kong, Taiwan, India, Singapore, and Malaysia. The drug is not available