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Published on: November 25, 2014
Ipsapirone and 1-(2-pyrimidinyl)-piperazine increase rat locus coeruleus noradrenergic activity
M K Sanghera1, J A Coke, H L Williams
1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9070.
Abstract:
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.
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