Summary
Mazindol, an anorexic drug, caused a large increase in brain 3, 4-dihydroxyphenylacetic acid (DOPAC) concentration in spiperone-pretreated rats. The increase was dose-related over a 1–10 mg/kg dose range of mazindol and was maximum within 1 hour after mazindol injection into rats pretreated 1 hour previously with spiperone. In spiperone-pretreated rats, mazindol accelerated the disappearance of dopamine after inhibition of dopamine synthesis byα-methyltyrosine. Mazindol apparently resembles amfonelic acid, methylphenidate, and cocaine in facilitating the impulse-mediated release of dopamine.
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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.11, 303–314 (1970).
Braestrup, C., Scheel-Kruger, J. Methylphenidate-like effects of the new antidepressant drug nomifensine (HOE 984). Eur. J. Pharmacol.38, 305–312 (1976).
Carruba, M. O., Groppetti, A., Mantegazza, P., Vicentini, L., Zambotti, F. Effects of mazindol, a non-phenylethylamine anorexigenic agent, on biogenic amine levels and turnover rate. Brit. J. Pharmacol.56, 431–436 (1976).
Chang, C. C. A sensitive method for spectrophotofluorometric assay of catecholamines. Int. J. Neuropharmacol.3, 643–649 (1964).
Fuller, R. W., Perry, K. W.: Effect of lergotrile on 3, 4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover in rat brain. J. Neural Transm. (in press).
Fuller, R. W., Perry, K. W., Bymaster, F. P., Wong, D. T.: Comparative effects of pemoline, amfonelic acid and amphetamine on dopamine uptake and releasein vitro and on brain 3, 4-dihydroxyphenylacetic acid concentration in spiperone-treated rats. J. Pharm. Pharmacol. (in press).
Gogerty, J. H., Penberthy, C., Iorio, L. C., Trapold, J. H. Pharmacologic analysis of a new anorexic substance: 5-hydroxy-5-(4′-chlorophenyl)-2, 3-dihydro-5H-imidazo-(2, 1-a)-isoindole (mazindol). Arch. int. Pharmacodyn.214, 285–307 (1975).
Heikkila, R. E., Cabbat, F. S., Mytilineou, C. Studies on the capacity of mazindol and dita to act as uptake inhibitors or releasing agents for3H-biogenic amines in rat brain tissue slices. Eur. J. Pharmacol.45, 329–333 (1977).
Jori, A., Dolfini, E. On the effect of anoretic drugs on striatum homovanillic acid in rats. Pharmacol. Res. Commun.6, 175–178 (1974).
Koe, B. K. Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J. Pharmacol. Exp. Ther.199, 649–661 (1976).
Kruk, Z. L., Zarrindast, M. R. Mazindol anorexia is mediated by activation of dopaminergic mechanism. Brit. J. Pharmacol.56, 367–372 (1976).
Murphy, G. F., Robinson, D., Sharman, D. F. The effect of tropolone on the formation of 3, 4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid in the brain of the mouse. Brit. J. Pharmacol.36, 107–115 (1969).
Ross, S. B. On the mode of action of central stimulatory agents. Acta pharmacol. toxicol.41, 392–396 (1977).
Shore, P. A. Actions of amfonelic acid and other non-amphetamine stimulants on the dopamine neuron. J. Pharm. Pharmacol.28, 855–857 (1976).
Spano, P. F., Neff, N. H. Procedure for the simultaneous determination of dopamine, 3-methoxy-4-hydroxyphenylacetic acid and 3, 4-dihydroxyphenylacetic acid in brain. Anal. Biochem.42, 113–118 (1971).
Zambotti, F., Carruba, M. O., Barzaghi, F., Vicentini, L., Groppetti, A., Mantegazza, P. Behavioural effects of a new non-phenylethylamine anorexigenic agent: mazindol. Eur. J. Pharmacol.36, 405–412 (1976).
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Fuller, R.W., Snoddy, H.D. Effect of mazindol on brain dopamine turnover in spiperone-treated rats. J. Neural Transmission 44, 13–19 (1979). https://doi.org/10.1007/BF01252698
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DOI: https://doi.org/10.1007/BF01252698