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Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat.

Rats were trained to discriminate the novel analgesic flupirtine (10.0 mg/kg i.p., 10 min) from no drug under a two-choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose-response curve with an ED50 of 3.87 mg/kg. The opioid analgesics pentazocine, codeine and tramadol failed to produce flupirtine appropriate responding. The opioid antagonist naltrexone did not antagonize the discriminative effects of flupirtine. The mixed alpha-1/alpha-2 adrenergic agonist clonidine and the highly specific alpha-2 adrenergic agonist UK-14304, both partially and dose-dependently produced flupirtine appropriate responding. The mixed alpha-1/alpha-2 antagonist yohimbine and the highly specific alpha-2 antagonists idazoxan and L-654,284 all partially and dose-dependently antagonized flupirtine appropriate responding. Neither of the alpha-1 agonists phenylephrine or ST 587 produced flupirtine appropriate responding, nor did the alpha-1 antagonist prazosin antagonize flupirtine responding. It is concluded that the discriminative effects of flupirtine are neither of opioid nor of alpha-1 adrenergic type, but are primarily mediated through alpha-2 adrenergic mechanisms.