title: Atipamezole, an alpha 2 antagonist, augments opiate-induced muscle rigidity in the rat.
abstract: Atipamezole is a new, highly selective alpha2-adrenoceptor antagonist currently undergoing clinical trials as an antagonist for dexmedetomidine, a potent alpha2 agonist with sedative and analgesic properties. It has previously been demonstrated that dexmedetomidine, acting at central alpha2 adrenoceptors, antagonizes opiate-induced muscle rigidity. However, the role of endogenous alpha2-adrenergic systems in opiate-induced rigidity remains to be elucidated. The present study was designed to assess the effects of atipamezole on basal muscle tone and on alfentanil-induced muscle rigidity in the rat. Muscle tone was measured using gastrocnemius electromyography (EMG). After a 15-min baseline, saline or atipamezole (0.3 or 1.0 mg/kg) was administered, and 10 min later, saline or alfentanil (50, 150, or 300 micrograms/kg) was injected subcutaneously. Data were collected for an additional 60 min. Atipamezole (1.0 mg/kg) pretreatment (in the absence of alfentanil) produced a small increase in tonic EMG activity when compared with saline pretreatment. After saline pretreatment, significant muscle rigidity occurred in the two highest alfentanil dose groups. Atipamezole (0.3 and 1.0 mg/kg) augmented alfentanil-induced muscle rigidity. The ability of the alpha2 antagonist to potentiate both basal muscle tone and alfentanil-induced rigidity suggests that endogenous adrenergic activity and/or direct alpha2-adrenoceptor interaction with opioid receptors mediate opiate-induced muscle rigidity. These findings may be of clinical as well as basic neuropharmacological interest.
authors.affiliation: Department of Anesthesiology, University of California, San Diego.
authors.forename: M B
authors.initials: MB
authors.lastname: Weinger
authors.forename: J M
authors.initials: JM
authors.lastname: Bednarczyk
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D015760:Alfentanil / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced* / Q000503:physiopathology; D009129:Muscle Tonus / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D007093:Imidazoles; D009294:Narcotics; C050701:atipamezole; D015760:Alfentanil