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.
Dabire
H
H
Dausse
J P
JP
Mouille
P
P
Fournier
B
B
Cardot
A
A
Meyer
P
P
Schmitt
H
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects; D002645:Chickens; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D019329:Idazoxan; D007536:Isomerism; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013569:Synapses / Q000502:physiology; D013610:Tachycardia / Q000139:chemically induced
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D006993:Hypnotics and Sedatives; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D019329:Idazoxan