An α2-AR antagonist and active metabolite of azapirones
2-(1-Piperazinyl)pyrimidine is an antagonist of α2-adrenergic receptors (α2-ARs; pA2 = 6.8 in rat brain synaptosomes) and active metabolite of various azapirones, including buspirone.1,2,3,4 It is formed from buspirone by the cytochrome P450 (CYP) isoform CYP3A4 in human liver microsomes.5 2-(1-Piperazinyl)pyrimidine inhibits decreases in gastrointestinal transit induced by clonidine in rats (ED50 = 0.8 mg/kg).2 It increases drinking in the Vogel punished drinking task, indicating anxiolytic-like activity, in rats when administered at doses ranging from 1 to 4 mg/kg.3 2-(1-Piperazinyl)pyrimidine (0.25-1 mg/kg) also reduces the amplitude of electrically stimulated excitatory post-synaptic potentials (EPSPs) in the hippocampal CA1 region in rats, an effect that can be blocked by the serotonin (5-HT) receptor subtype 5-HT1A antagonist spiroxatrine.4 It has also been used a phosphopeptide derivatization agent.6
1.Gobbi, M., Frittoli, E., and Mennini, T.Antagonist properties of 1-(2-pyrimidinyl)piperazine at presynaptic α2-adrenoceptors in the rat brainEur. J. Pharmacol.180(1)183-186(1990) 2.Bianchi, G., Caccia, S., Della Vedova, F., et al.The α2-adrenoceptor antagonist activity of ipsapirone and gepirone is mediated by their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP)Eur. J. Pharmacol.151(3)365-371(1988) 3.Gower, A.J., and Tricklebank, M.D.α2-adrenoceptor antagonist activity may account for the effects of buspirone in an anticonflict test in the ratEur. J. Pharmacol.155(1-2)129-137(1988) 4.Manahan-Vaughan, D., Anwyl, R., and Rowan, M.J.The azapirone metabolite 1-(2-pyrimidinyl)piperazine depresses excitatory synaptic transmission in the hippocampus of the alert rat via 5-HT1A receptorsEur. J. Pharmacol.294(2-3)617-624(1995) 5.Zhu, M., Zhao, W., Jimenez, H., et al.Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomesDrug Metab. Dispos.33(4)500-507(2005) 6.Zhang, L., Xu, Y., Lu, H., et al.Carboxy group derivatization for enhanced electron-transfer dissociation mass spectrometric analysis of phosphopeptidesProteomics9(16)4093-4097(2009)
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