Pharmacological evidence for the involvement of 1-(2-pyridinyl)-piperazine (1-PmP) in the interaction of buspirone or gepirone with noradrenergic systems.
We investigated in mice the effects of one of the principal metabolites of buspirone and gepirone, 1-(2-pyridinyl)-piperazine (1-PmP), on hypothermia and reduced locomotion induced by clonidine (0.25 and 0.06 mg/kg, respectively), tests related to brain alpha-adrenergic function. Both effects were antagonized dose dependently by 1-PmP (1-16 mg/kg i.p.). Moreover, pretreatment with proadifen (50 mg/kg) prevented the reversal by buspirone and gepirone of clonidine-induced hypothermia. This suggests that 1-PmP could be responsible for some of the apparent noradrenergic effects of buspirone and gepirone.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D002065:Buspirone / Q000031:analogs & derivatives; D003000:Clonidine / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; C052140:1-(2-pyridinyl)piperazine; C039979:gepirone; D003000:Clonidine; D002065:Buspirone