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

Abstract

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.

• Authors: H Dabire, J P Dausse, P Mouille, B Fournier, A Cardot, P Meyer, H Schmitt
• Journal: Clinical and experimental hypertension. Part A, Theory and practice (Clin Exp Hypertens A) Vol. 8 Issue 3 Pg. 387-409 ( 1986) ISSN: 0730-0077 [Print] United States
• PMID: 2873908 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenergic alpha-Antagonists
• Dioxanes
• Dioxins
• Hypnotics and Sedatives
• Receptors, Adrenergic, alpha
• Clonidine
• Idazoxan

Topics

• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Binding, Competitive
• Blood Pressure (drug effects)
• Cerebral Cortex (drug effects)
• Chickens
• Clonidine (pharmacology)
• Decerebrate State
• Dioxanes (pharmacology)
• Dioxins (pharmacology)
• Dogs
• Electric Stimulation
• Female
• Heart Rate (drug effects)
• Hypnotics and Sedatives (pharmacology)
• Idazoxan
• Isomerism
• Male
• Neural Inhibition (drug effects)
• Rats
• Rats, Inbred Strains
• Receptors, Adrenergic, alpha (drug effects)
• Synapses (physiology)
• Tachycardia (chemically induced)