Disposition of the Psychotropic Drugs Buspirone, MJ-13805 and Piribedil, and of Their Common Active Metabolite 1-(2-pyrimidinyl)-piperazine in the Rat

1-(2-Pyrimidinyl)-piperazine (PmP) is a common metabolite of the structurally related drugs buspirone, MJ-13805 and piribedil. After i.v. injection (25 mumol/kg) to rats, all three parent drugs are rapidly cleared with a t 1/2 (beta) of about 30 min. The metabolite t 1/2 is about four times that of its parent drugs. 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. Results indicate that PmP formation is a pharmacologically significant process for both buspirone and MJ-13805 but it is probably less important for piribedil.