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Specificity of the dopamine sensitive adenylate cyclase for anti psychotic antagonists


, : Specificity of the dopamine sensitive adenylate cyclase for anti psychotic antagonists. Life Sciences 19(6): 927-934

Chlorpromazine, haloperidol and clozapine are approximately equipotent in antagonizing dopamine sensitive adenylate cyclase activity in homogenates of rat brain striatum. The antagonism appeared to occur at a structurally specific dopamine site, as inhibition by a series of chlorpromazine analogues of similar hydrophobicity exhibited a structural specificity similar to that found for their neuroleptic and cataleptic activities. Sulpiride, a dopamine antagonist with antipsychotic activity, and metochlopramide, a structurally related central dopamine antagonist, failed to inhibit the dopamine sensitive adenylate cyclase. Pretreatment of rats with haloperidol (3 mg/kg per day) for 6 or 28 days did not induce a supersensitive response of the adenylate cyclase to stimulation by dopamine or apomorphine or inhibition by clozapine. The dopamine sensitive adenylate cyclase may not be the site of action of all antipsychotic agents.

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Accession: 006459034

PMID: 966971

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Related references

Roufogalis B.D.; Thornton M.; Wade D.N., 1976: Sulpiride a new anti psychotic agent and metoclopramide a central dopamine antagonist do not inhibit dopamine sensitive adenylate cyclase in rat brain. Canadian Federation of Biological Societies Proceedings 19: 48

Clement Cormier Y.C., 1978: Dopamine sensitive adenylate cyclase from the median eminence the role of anti psychotic drugs. George, William J And Louis J Ignarro (Ed ) Advances in Cyclic Nucleotide Research, Vol 9 Third International Conference on Cyclic Nucleotides New Orleans, La , Usa, July 17-22, 1977 Xxxii+799p Illus Raven Press: New York, N Y , Usa Isbn 0-89004-240-3 735-736

Racagni, G.; Carenzi, A., 1976: The anterior amygdala dopamine sensitive adenylate cyclase point of action of anti psychotic drugs. An adenylate cyclase specifically stimulated by dopamine [DA], was identified in the anterior amygdaloid area. This enzyme showed kinetic properties very similar to that described for the DA dependent adenylate cyclase in the rat caudate nucleus....

Sheppard H.; Burghardt C.R., 1974: The dopamine sensitive adenylate cyclase of rat caudate nucleus part 1 comparison with the isoproterenol sensitive adenylate cyclase beta receptor system of rat erythrocytes in responses to dopamine derivatives. Molecular Pharmacology 10(5): 721-726

Greengard P., 1976: The action of anti psychotic drugs on dopamine stimulated adenylate cyclase activity. Sedvall, Goran, Borje Uvnas And Yngve Zotterman (Ed ) Wenner-Gren Center International Symposium Series, Vol 25 Antipsychotic Drugs: Pharmacodynamics And Pharmacokinetics Stockholm, Sweden, Sept 17-19, 1974 Ix+459p Illus Pergamon Press: Oxford, England; New York, N Y , Usa Isbn 0-08-019688-8 271-283

Sheppard, H.; Burghardt, C.R.; Teitel, S., 1976: The dopamine-sensitive adenylate cyclase of the rat caudate nucleus. II. A comparison with the isoproterenol-sensitive (beta) adenylate cyclase of the rat erythrocyte for inhibition or stimulation by tetrahydroisoquinolines. Molecular Pharmacology 12(5): 854-861

Burkard W.P., 1978: Specificity of histamine sensitive adenylate cyclase and its blockade by h 2 receptor antagonists. Experientia (Basel) 34(7): 922

Sheppard, H.; Burghardt, C.R.; Teitel, S., 1976: The dopamine sensitive adenylate cyclase of the rat caudate nucleus part 2 a comparison with the isoproterenol sensitive beta adenylate cyclase of the rat erythrocyte for inhibition or stimulation by tetra hydro iso quinolines. Tetrahydroisoquinoline (THI) derivatives were tested for agonist and antagonist activity with dopamine and .beta. adenylate cyclase systems. Agonist activity, seen only with the .beta. cyclase, was associated with hydroxyl groups at the positions...

Miller, R., 1975: Inhibition of dopamine-sensitive adenylate cyclase in rat basal ganglia and other hormone sensitive adenylate cyclase systems by neuroleptic drugs. British Journal of Pharmacology 53(3): 457p-458p

Watling, K.J.; Woodruff, G.N.; Poat, J.A., 1979: Dopamine-sensitive adenylate cyclase in homogenates of rat nucleus accumbens: structure-activity studies and effects of agonists and antagonists. A study has been made of the structural requirements for activity on the dopamine-sensitive adenylate cyclase present in homogenates of rat nucleus accumbens. The only active phenylethylamine derivatives tested were those containing hydroxy groups...