Motor effects of (-)-OSU6162 in primates with unilateral 6-hydroxydopamine lesions

Eur J Pharmacol. 2000 Feb 18;389(2-3):193-9. doi: 10.1016/s0014-2999(99)00879-1.

Abstract

The effects of the novel compound, (-)-OSU6162 ((S)-(-)-3-methylsulfonylphenyl-1-propylpiperidine), on rotational behavior induced by dopamine receptor agonists was investigated in common marmosets (Callithrix jacchus) with unilateral 6-hydroxydopamine lesions. (-)-OSU6162 per se displayed no effect on the animals' behavior. On the other hand, pretreatment with (-)-OSU6162 attenuated rotational behavior induced by apomorphine (apomorphini hydrochloridum), L-DOPA (3,4-dihydroxyphenylalanine), and the dopamine D2 receptor agonist, quinpirole (trans-(-)-4aR-4,4a, 5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolol[3,4-g]quinoline hydrochloride), without inducing motor impairment such as akinesia or dystonia. In addition, treatment with (-)-OSU6162 for 5 consecutive days almost completely abolished the rotational behavior provoked by apomorphine and produced a transient subsensitization of such apomorphine-induced effects after it was discontinued. Moreover, pretreatment with (-)-OSU6162 in two monkeys augmented the rotational behavior elicited by the dopamine D1 receptor agonists, SKF-81297 (R(+)-6-chloro-7,8,dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrobromide) and A-77636 ((-)-(1R, 3S)-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5, 6-dihydroxy-1H-2-benzopyran hydrochloride). The findings indicate that (-)-OSU6162 can exert indirect state-dependent effects that differentially affect dopamine D1 and dopamine D2 receptor agonist-induced behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Benzazepines / pharmacology
  • Benzopyrans / pharmacology
  • Callithrix
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Levodopa / pharmacology
  • Male
  • Motor Activity / drug effects*
  • Oxidopamine
  • Parkinson Disease / drug therapy*
  • Piperidines / pharmacology*
  • Quinpirole / pharmacology
  • Rotation

Substances

  • Benzazepines
  • Benzopyrans
  • Dopamine Antagonists
  • Piperidines
  • OSU 6162
  • A 77636
  • Quinpirole
  • Levodopa
  • SK&F 81297
  • Oxidopamine
  • Apomorphine
  • Adamantane