Ipsapirone and 1-(2-pyrimidinyl)-piperazine increase rat locus coeruleus noradrenergic activity.
The effects of systemically administered ipsapirone, an aryl-piperazine compound, and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), on locus coeruleus (LC) noradrenergic activity was investigated. On an equimolar basis both ipsapirone and 1-PP were approximately equipotent in increasing LC neuronal activity. However, pretreatment with 1-PP caused a significantly greater parallel shift to the right of the dose response curve for the inhibitory action of the LC alpha 2-receptor agonist clonidine compared to ipsapirone. Biochemically, pretreatment with SKF 525A, a compound which prevents the formation of 1-PP from ipsapirone, diminished the ipsapirone-induced increase in MOPEG-SO4 levels in the brainstem and cortex. These data, together with the findings that 1-PP is more potent than ipsapirone in displacing 3H-clonidine from cerebral cortical membranes, suggest that the parent drug influences LC neuronal activity via the action of I-PP on LC alpha 2-adrenoceptors.
Sanghera
M K
MK
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9070.
Coke
J A
JA
Williams
H L
HL
McMillen
B A
BA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002065:Buspirone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011743:Pyrimidines; C043077:ipsapirone; C037921:1-(2-pyrimidinyl)piperazine; D003000:Clonidine; D002065:Buspirone; D009638:Norepinephrine