Trihexyphenidyl Interactions with the Dopamine D1-Selective Receptor Agonist SKF-82958 and the D2-Selective Receptor Agonist N-0923 in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Hemiparkinsonian Monkeys1

  1. Edward F. Domino and
  2. Lisong Ni
  1. Department of Pharmacology, University of Michigan, Ann Arbor, Michigan

    Abstract

    The effects of the antiparkinsonian agent trihexyphenidyl, a selective M1 muscarinic cholinergic receptor antagonist, were studied in doses of 100, 320 and 1000 μg/kg i.m. alone. Trihexyphenidyl was then studied in combination with the selective dopamine receptor D1 agonist SKF-82958 [(±)-6-chloro-7–8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzazepine hydrobromide] and the selective D2 agonist N-0923 [(−)2-(N-propyl-N-2-thienylethyl)amino-5-hydroxytetralin HCl] on rotational behavior in five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned hemiparkinsonian monkeys. Given alone, trihexyphenidyl had no effect on ipsiversive and slightly enhanced contraversive circling. Contraversive circling produced by 74.8 and 234 μg/kg SKF-82958 i.m. was potentiated by increasing doses of trihexyphenidyl. On the other hand, contraversive circling produced by 10 and 32 μg/kg N-0923 i.m. was progressively reduced with increasing doses of trihexyphenidyl. The results obtained indicate differential actions on circling behavior between a selective M1 muscarinic cholinergic receptor antagonist and selective D1 and D2 receptor agonists in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of hemiparkinsonism.

    Footnotes

    • Send reprint requests to: Dr. E. F. Domino, Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109-0632.

    • ↵1 This work was supported in part by Psychopharmacology Research Fund 361024.

    • ↵2 E. F. Domino, unpublished observations.

    • Abbreviations:
      6-OHDA
      6-hydroxydopamine
      MPTP
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      i.m.
      intramuscularly
      DA
      dopamine
      mAChR
      muscarinic cholinergic receptor
      NMDA
      N-methyl-d-aspartate
      ACh
      acetylcholine
      • Received May 21, 1997.
      • Accepted September 15, 1997.
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    1. JPET January 1, 1998 vol. 284 no. 1 307-311
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