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Pharmacological properties of the enantiomers of idazoxan: possible separation between their alpha-adrenoceptor blocking effects.

The alpha-adrenoceptor blocking properties of the two enantiomers of idazoxan have been investigated in rats, dogs and chicks, as well as their agonistic effects in pithed rats. At peripheral sites, (+) idazoxan was equipotent for blocking both postsynaptic alpha-1 and alpha-2 adrenoceptors of the rat and revealed to be a potent antagonist at presynaptic sites of rats and dogs. (-) Idazoxan revealed to be selective for postsynaptic alpha-2 adrenoceptors with an apparent selectivity ratio of about 10. This selectivity of (-) idazoxan was greater in vitro. (-) Idazoxan also antagonized presynaptic alpha-2 adrenoceptors of rats and dogs. At central sites, (+) and (-) idazoxan antagonized the hypotension, bradycardia, inhibition of sympathetic nerve activity induced by clonidine in rats and dogs and sedation induced by clonidine and azepexole in chicks. Although (+) idazoxan was more potent than (-) idazoxan, binding studies revealed (-) idazoxan to be more selective than (+) idazoxan at central sites. It is concluded that (+) idazoxan antagonizes both alpha-1 and alpha-2 adrenoceptors and (-) idazoxan is selective for alpha-2 adrenoceptors. In the pithed rat, only (-) idazoxan possesses both alpha-1 and alpha-2 agonistic effects. These results show little differences between the two enantiomers of idazoxan as for those of imidazoline derivatives.