Disposition of the psychotropic drugs buspirone, MJ-13805 and piribedil, and of their common active metabolite 1-(2-pyrimidinyl)-piperazine in the rat

Abstract

1. 1-(2-Pyrimidinyl)-piperazine (PmP) is a common metabolite of the structurally related drugs buspirone, MJ-13805 and piribedil.

2. After i.v. injection (25 μmol/kg) to rats, all three parent drugs are rapidly cleared with a t_1/2 (β) of about 30 min. The metabolite t_1/2 is about four times that of its parent drugs.

3. About 25, 23 and 2% of buspirone, MJ-13805 and piribedil, respectively, reaches the systemic circulation as PmP. The metabolite concentrates in the brain where its A.U.C. is about twice those of buspirone and MJ-13805.

4. Results indicate that PmP formation is a pharmacologically significant process for both buspirone and MJ-13805 but it is probably less important for piribedil.