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.
Koller
W
W
Department of Neurology, Loyola-Hines Medical Center, Maywood, Illinois.
Herbster
G
G
Gordon
J
J
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D015259:Dopamine Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D010078:Oxazines / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D015259:Dopamine Agents; D010078:Oxazines; D011954:Receptors, Dopamine; C042631:naxagolide