Automated method for the measurement of fentanyl-induced muscular rigidity.
An automated method is described that can accurately and reliably measure weight displacement resulting from hindlimb extension due to muscular rigidity following opioid administration in rats. IV administration of fentanyl (0.035 mg/kg) immediately induced rigidity. Rigidity was dose dependently reversed by the alpha 2-agonist clonidine with an ED50 value equal to 0.011 mg/kg IV. Second, rigidity was restored following administration of the alpha 2-antagonist idazoxan (0.3 mg/kg, IV) thereby confirming an alpha 2-mediated mechanism of action. Previously, reversal of fentanyl-induced muscular rigidity was measured by subjective rating criteria not suitable for quantitative potency comparisons. The new automated rigidity model provides a simple yet precise measurement of the ability of alpha 2-agonists to attenuate opioid-induced muscular rigidity in rats.
Del Vecchio
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CNS Pharmacology, Anaquest Inc., Murray Hill, NJ 10974.
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D019329:Idazoxan; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced / Q000503:physiopathology*; D010827:Physiology / Q000295:instrumentation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects
D058669:Adrenergic alpha-2 Receptor Antagonists; D004146:Dioxanes; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D005283:Fentanyl; D019329:Idazoxan