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Docarpamine
Docarpamine (INN, JAN), sold under the brand name Tanadopa, is an orally active dopamine prodrug which is marketed in Japan for the treatment of acute cardiac insufficiency and/or chronic heart failure.[2][3][4][5][6] It is used orally and intravenously.[1] In terms of bioactivation, the hydroxyl groups of docarpamine are freed by esterases in the gut and liver and the amino group is freed by γ-glutamyltransferase in the kidney and liver.[5][1][7] There is an intermediate, dideethoxycarbonyldocarpamine (DECD), in which the hydroxyl substitutions have been hydrolyzed.[1] The N-substitution protects the drug from first-pass metabolism by monoamine oxidase (MAO) until it is cleaved into dopamine and allows it to be orally active.[6][7] The drug does not cross the blood–brain barrier or affect the central nervous system even at high doses and hence is peripherally selective.[1][8][3] The predicted log P (XLogP3) of docarpamine is 2.9.[9] It is thought that the therapeutic effects of docarpamine are mediated by activation of peripheral dopamine D1 receptors.[3] Although docarpamine is orally active and can achieve therapeutic levels of dopamine in blood,[1] relatively high doses and frequent administration of the drug (e.g., 600–750 mg every 8 hours) are required when it is used by this route.[5][4][10] Its duration of action orally is described as greater than 4 hours.[4] The drug was first described in the scientific literature by 1980.[2] See alsoReferences
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