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. 1975 May;54(1):115–121. doi: 10.1111/j.1476-5381.1975.tb07417.x

The interaction of neuroleptic and muscarinic agents with central dopaminergic systems.

P H Kelly, R J Miller
PMCID: PMC1666384  PMID: 1139072

Abstract

1. The effect of muscarinic and neuroleptic agents on the turning behaviour induced by methamphetamine and apomorphine in rats with unilateral lesions of the substantia nigra induced by 6-hydroxydopamine has been examined. 2. Turning towards the side of the lesion induced by (+)-methamphetamine (5 mg/kg) was inhibited by alpha-flupenthixol (1 mg/kg) and alpha-clopenthixol (8 mg/kg) but not by high doses of their beta-isomers. 3. Turning was inhibited by chlorpromazine (4 mg/kg) and pimozide (0.2 mg/kg). Thioridazine and clozapine (16 mg/kg) were ineffective. Turning in the same direction produced by scopolamine (10 mg/kg) was also inhibited by alpha-flupenthixol (1 mg/kg) and pimozide (0.25 mg/kg). 4. Turning produced by methamphetamine (5 mg/kg) was inhibited by oxotremorine (0.75 mg/kg) even in the presence of methylatropine (5 mg/kg). 5. Turning away from the side of the lesion induced by apomorphine (0.1 mg/kg) was inhibited by oxotremorine (0.75 mg/kg) but not by thioridazine or clozapine (16 mg/kg). 6. These results are discussed with regard to the mode of action of neuroleptic drugs in producing anti-psychotic effects and drug-induced Parkinsonism.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andén N. E., Butcher S. G., Corrodi H., Fuxe K., Ungerstedt U. Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur J Pharmacol. 1970;11(3):303–314. doi: 10.1016/0014-2999(70)90006-3. [DOI] [PubMed] [Google Scholar]
  2. Bürki H. R., Ruch W., Asper H., Baggiolini M., Stille G. Pharmakologische und neurochemische Wirkungen von Clozapin: neue Gesichtspunkte in der medikamentösen Behandlung der Schizophrenie. Schweiz Med Wochenschr. 1973 Dec 1;103(48):1716–1724. [PubMed] [Google Scholar]
  3. COLE J. O., CLYDE D. J. Extrapyramidal side effects and clinical response to the phenothiazines. Rev Can Biol. 1961 Jun;20:565–574. [PubMed] [Google Scholar]
  4. Clement-Cormier Y. C., Kebabian J. W., Petzold G. L., Greengard P. Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1113–1117. doi: 10.1073/pnas.71.4.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Costall B., Naylor R. J., Olley J. E. Catalepsy and circling behaviour after intracerebral injections of neuroleptic, cholinergic and anticholinergic agents into the caudate-putamen, globus pallidus and substantia nigra of rat brain. Neuropharmacology. 1972 Sep;11(5):645–663. doi: 10.1016/0028-3908(72)90073-1. [DOI] [PubMed] [Google Scholar]
  6. Crow T. J., Gillbe C. Dopamine antagonism and antischizophrenic potency of neuroleptic drugs. Nat New Biol. 1973 Sep 5;245(140):27–28. doi: 10.1038/newbio245027a0. [DOI] [PubMed] [Google Scholar]
  7. Horn A. S., Cuello A. C., Miller R. J. Dopamine in the mesolimbic system of the rat brain: endogenous levels and the effects of drugs on the uptake mechanism and stimulation of adenylate cyclase activity. J Neurochem. 1974 Feb;22(2):265–270. doi: 10.1111/j.1471-4159.1974.tb11589.x. [DOI] [PubMed] [Google Scholar]
  8. Hornykiewicz O. Dopamine in the basal ganglia. Its role and therapeutic implications (including the clinical use of L-DOPA). Br Med Bull. 1973 May;29(2):172–178. doi: 10.1093/oxfordjournals.bmb.a070990. [DOI] [PubMed] [Google Scholar]
  9. Javoy F., Agid Y., Bouvet D., Glowinski J. Changes in neostriatal DA metabolism after carbachol or atropine microinjections into the substantia nigra. Brain Res. 1974 Mar 22;68(2):253–260. doi: 10.1016/0006-8993(74)90394-1. [DOI] [PubMed] [Google Scholar]
  10. Miller R. J., Hiley C. R. Anti-muscarinic properties of neuroleptics and drug-induced Parkinsonism. Nature. 1974 Apr 12;248(449):596–597. doi: 10.1038/248596a0. [DOI] [PubMed] [Google Scholar]
  11. Sethy V. H., Van Woert M. H. Regulation of striatal acetylcholine concentration by dopamine receptors. Nature. 1974 Oct 11;251(5475):529–530. doi: 10.1038/251529a0. [DOI] [PubMed] [Google Scholar]
  12. Shintomi K., Yamamura M. Letter: Effects of antiparkinsonian drugs on neuroleptic-induced extrapyramidal signs in monkeys. J Pharm Pharmacol. 1973 Aug;25(8):666–667. doi: 10.1111/j.2042-7158.1973.tb10661.x. [DOI] [PubMed] [Google Scholar]
  13. Snyder S., Greenberg D., Yamamura H. I. Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry. 1974 Jul;31(1):58–61. doi: 10.1001/archpsyc.1974.01760130040006. [DOI] [PubMed] [Google Scholar]
  14. Stadler H., Lloyd K. G., Gadea-Ciria M., Bartholini G. Enhanced striatal acetylcholine release by chlorpromazine and its reversal by apomorphine. Brain Res. 1973 Jun 15;55(2):476–480. doi: 10.1016/0006-8993(73)90317-x. [DOI] [PubMed] [Google Scholar]
  15. Ungerstedt U., Arbuthnott G. W. Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res. 1970 Dec 18;24(3):485–493. doi: 10.1016/0006-8993(70)90187-3. [DOI] [PubMed] [Google Scholar]

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