Abstract—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 ethylmorphineN‐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 α2‐adrenoceptor antagonism of ipsapirone in rats and that chronic treatment with the drug does not affect its biotr