PHNO, a novel dopamine agonist, in animal models of parkinsonism

PHNO, a naphthoxazine compound, was investigated in animal models of central dopaminergic activity. The drug in doses of 5-300 micrograms/kg when administered subcutaneously, or transdermally, induced stereotypic behavior in rats which was blocked by haloperidol but not by reserpine pretreatment. In rats with unilateral 6-hydroxydopamine lesions of the substantia nigra PHNO induced dose-dependent contralateral turnings. The drug caused emesis in dogs and hypothermia in mice. PHNO bound to D-2 dopamine receptors in the rat striatum. Chronic injection with PHNO did not induce behavioral supersensitivity or increase dopamine receptor density. These data indicate that PHNO is a direct acting dopamine agonist that is highly potent. PHNO differs from other dopaminergic drugs and may be useful in the treatment of Parkinson's disease.