Cerebral pharmacokinetics of ipsapirone in rats after different routes of administration.
Ipsapirone, a putative non-benzodiazepine anxiolytic, was extensively metabolized in rats to 1-(2-pyrimidinyl)piperazine (1-PP) which accumulated in the brain. Neither the route of administration (i.p. or p.o.), nor prolonged administration of ipsapirone or 1-PP affected their accumulation in the rat brain. The cytochrome P450 level and ethylmorphine N-demethylase activity in rat liver microsomes were unchanged by chronic treatment with ipsapirone or 1-PP. The results indicate that 1-PP may contribute to the alpha 2-adrenoceptor antagonism of ipsapirone in rats and that chronic treatment with the drug does not affect its biotransformation to 1-PP.
Nocon
H
H
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Daniel
W
W
Danek
L
L
Melzacka
M
M
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D006207:Half-Life; D007274:Injections, Intraperitoneal; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011335:Proadifen / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; C043077:ipsapirone; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D005037:Ethylmorphine-N-Demethylase; C039979:gepirone