Abstract
Tremor produced in laboratory mice by the benzylimidoylurea derivative LON 954 was potentiated in a dose-dependent manner by a variety of typical and atypical neuroleptics. The most effective agents in this respect were those shown by other workers to have a selective action at dopamine receptors, notably the butyrophenones, thioxanthines and fluphenazine. Chlorpromazine and prochlorperazine produced inconsistent effects while clozapine and loxapine respectively delayed and prolonged the peak tremor response. While these findings support primary involvement of striatal dopaminergic mechanisms in LON 954 tremorogenesis, a reduction in cyclic AMP levels may be an important factor in the observed effects.
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Andén, N. E., Butcher, S., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur. J. Pharmacol. 11, 303–314 (1970)
Bürki, H. R., Ruch, W., Asper, H.: Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacologia (Berl.) 41, 27–33 (1975)
Costall, B., Naylor, R. J.: Neuroleptic antagonism of dyskinetic phenomena. Eur. J. Pharmacol. 33, 301–312 (1975)
Costall, B., Naylor, R. J.: A comparison of the abilities of typical neuroleptic agents and of thioridazine, clozapine, sulpiride and metoclopramide to antagonise the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems. Eur. J. Pharmacol. 40, 9–19 (1976)
Coward, D. M., Doggett, N. S., Sayers, A. C.: The pharmacology of LON 954 [N-carbamoyl,2-(2,6-dichlorophenyl) acetamidine hydrochloride] — a new tremorogenic agent. Arzneim. Forsch. 27, 2326–2332 (1977a)
Coward, D. M., Doggett, N. S., Thomas, J. E.: Central transmitter involvement in LON 954-induced tremorogenesis. Neuropharmacology 16, 479–484 (1977b)
Coward, D. M., Doggett, N. S.: The production of an alternative laboratory model of the Parkinson syndrome using a new benzylimidoylurea derivative, LON 954. Psychopharmacology 52, 165–171 (1977)
De Maio, D.: Pteliminary clinical evaluation of a new neuroleptic agent: HF-1854. In: The present status of psychotropic drugs. Psychopharmacological and clinical aspects, pp. 485–488. Amsterdam: Exerpta Medica Foundation 1969
Dolphin, A., Jenner, P., Marsden, C. D., Pycock, C., Tarsy, D.: Pharmacological evidence for cerebral dopamine receptor blockade by metoclopramide in rodents. Psychopharmacology 41, 133–138 (1979)
Greengard, P.: The action of antipsychotic drugs on dopaminestimulated adenylate cyclase activity. In: Antipsychotic drugs: Pharmacodynamics and pharmacokinetics. G. Sedvall, B. Unväs, Y. Zolterman, eds., pp. 271–283. Oxford: Pergamon 1974
Iversen, L. L., Horn, A. S., Miller, R. J.: Structure activity relationships for interactions of agonist and antagonist drugs with dopamine-stimulated adenylate cyclase of rat brain — a model for CNS dopamine receptors? In: Antipsychotic drugs: Pharmacodynamics and pharmacokinetics. G. Sedvall, B. Unväs, Y. Zolterman, eds., pp. 285–303. Oxford: Pergamon 1974
Roufogalis, B. D., Thornton, M., Wade, D. N.: Specificity of the dopamine-sensitive adenylate cyclase for anti-psychotic antagonists. Life Sci. 19, 927–934 (1976)
Walters, H. R., Roth, R. H.: Pre- and post-synaptic actions of antipsychotic drugs. In: Antipsychotic drugs: Pharmacodynamics and pharmacokinetics, G. Sedvall, B. Unväs, Y. Zolterman, eds., pp. 147–160. Oxford: Pergamon 1974
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Coward, D.M., Doggett, N.S. Potentiation of LON 954 tremor by typical and atypical neuroleptics — an indication of striatal dopamine antagonism. Psychopharmacology 67, 177–180 (1980). https://doi.org/10.1007/BF00431974
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DOI: https://doi.org/10.1007/BF00431974