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

Mov Disord. 1987;2(3):193-9. doi: 10.1002/mds.870020306.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Dopamine Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Injections, Subcutaneous
  • Male
  • Oxazines / therapeutic use*
  • Parkinson Disease, Secondary / drug therapy*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects
  • Stereotyped Behavior / drug effects

Substances

  • Dopamine Agents
  • Oxazines
  • Receptors, Dopamine
  • naxagolide