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Saari, W.S. et al.

Pyridinylpiperazines, a new class of selective alpha 2-adrenoceptor antagonists.

A series of 1-(2-pyridinyl)piperazine derivatives was synthesized and evaluated for adrenergic activity. In vitro activity was assessed through the antagonism of clonidine's effect in the rat, isolated, field-stimulated vas deferens and by the displacement of [3H]clonidine from membrane binding sites of calf cerebral cortex. Antagonism of clonidine-induced mydriasis in the rat was used as an in vivo assay. Several members of the series proved to be potent, selective alpha 2-adrenoceptor antagonists. 1-(3-Fluoro-2-pyridinyl)piperazine was more potent than either yohimbine or rauwolscine in displacement of [3H]clonidine and had a higher affinity for this binding site (alpha 2) than for the [3H]prazosin site (alpha 1). In vivo, the 3-F derivative was more potent than the reference standards in reversing clonidine-induced mydriasis. None of the members of this series was more selective or potent than rauwolscine in antagonizing clonidine in the rat vas deferens.[1]

References

Pyridinylpiperazines, a new class of selective alpha 2-adrenoceptor antagonists. Saari, W.S., Halczenko, W., King, S.W., Huff, J.R., Guare, J.P., Hunt, C.A., Randall, W.C., Anderson, P.S., Lotti, V.J., Taylor, D.A. J. Med. Chem. (1983) [Pubmed]

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