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.
Caccia
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Fong
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Guiso
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002065:Buspirone / Q000031:analogs & derivatives; D007700:Kinetics; D008297:Male; D010879:Piperazines / Q000378:metabolism*; D010891:Piribedil / Q000378:metabolism*; D011485:Protein Binding; D011743:Pyrimidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D014151:Anti-Anxiety Agents; D001798:Blood Proteins; D010879:Piperazines; D011743:Pyrimidines; D010891:Piribedil; C037921:1-(2-pyrimidinyl)piperazine; C039979:gepirone; D002065:Buspirone