An in vivo alpha-2 assay reversal of opioid-induced muscular rigidity and neuroleptic-induced ptosis

A method is described to detect selective α-2 adrenergic agonists in vivo. Palpebral ptosis is induced in rats by the neuroleptic agent haloperidol (Hal), or by tetrabenazine (TBZ) methanesulfonate. Twenty minutes later, test compounds are injected, and ptosis is scored. In a separate test, muscular rigidity is induced by the opioid, fentanyl, and subsequently, test compounds are assessed for their ability to reverse muscular rigidity. Results indicate that only α-2 agonists reliably reverse neuroleptic-induced and TBZ-induced ptosis, as well as opioid-induced rigidity. An α-1 antagonist reversed only rigidity, whereas, α-2 antagonists and β-agonists were generally ineffective in all tests. Therefore, the ability to reverse neuroleptic and TBZ-induced ptosis along with the ability to reverse opioid-induced muscular rigidity is a characteristic unique to α-2 agonists.