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Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain

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Summary

The effect of two calcium antagonists, nimodipine and flunarizine, on striatal dopamine (DA) metabolism in rats was compared. Flunarizine (5–20 mg/kg i.p.) caused a dose-dependent increase in the DA metabolite, 3,4-dihydroxyphenilacetic acid (DOPAC) in the caudate nucleus. Following the 20 mg/kg dose, DOPAC levels were maximally elevated by about 50% from 2 to 12 hrs after treatment.

On the contrary, nimodipine at the dose of 20 mg/kg i.p. produced a modest decrease in DOPAC levels. Neither calcium antagonist modified DA content.

However, both nimodipine and flunarizine, at the dose of 20 mg/kg, markedly reduced the accumulation of DOPAC in the caudate nucleus induced by haloperidol (1 mg/kg). It is suggested that flunarizine, but not nimodipine, has a neuroleptic-like action, whereas the two calcium antagonists have in common the ability to attenuate the hyperactivity of DA neurons.

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References

  • Carlsson A (1975) Receptor-mediated control of dopamine metabolism. In; Usdin E, Bunney WE Jr (eds) Pre- and postsynaptic receptors. M Dekker, New York, pp 49–65

    Google Scholar 

  • Chouza C, Caamano JL, Aljanti R, Scaramelli A, DeMedina O, Romero S (1986) Parkinsonism, tardive dyskinesia, akatisia, and depression induced by flunarizine. Lancet i: 1303–1304

    Google Scholar 

  • Cronin MJ (1982) Some calcium and lysosome antagonist inhibit 3H-spiperone binding to the porcine anterior pituitary. Life Sci 30: 1385–1389

    PubMed  Google Scholar 

  • Dubovsky SL, Franks RD, Lifschitz M, Coen P (1982) Effectiveness of Verapamil in the treatment of a maniac patient. Am J Psychiatry 139: 502–504

    PubMed  Google Scholar 

  • Gluskin LE, Strasberg B, Shah JH (1981) Verapamil-induced hyperprolactinemia and galactorrhea. Ann Intern Med 95: 66–67

    PubMed  Google Scholar 

  • Gould RJ, Murphy KMM, Reynolds IJ, Snyder SH (1983) Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists. Proc Natl Acad Sci USA 80: 5122–5125

    PubMed  Google Scholar 

  • Gould RJ, Murphy KMM, Reynolds IJ, Snyder SH (1984) Calcium channel blockade: Possible explanation for thioridazine's peripheral side effects. Am J Psychiaty 141: 352–357

    Google Scholar 

  • Grebb AJ (1986) Nifedipine and flunarizine block amphetamine-induced behavioral stimulation in mice. Life Sci 38: 2375–2382

    PubMed  Google Scholar 

  • Grebb AJ, Shelton C, Taylor EH, Bigelow LB (1986) A negative, double blind, placebocontrolled, clinical trial of verapamil in chronic schizophrenia. Biol Psychiatry 21: 691–694

    PubMed  Google Scholar 

  • Grebb AJ, Shelton RC, Freed WJ (1987) Diltiazem or verapamil prevents haloperidol-induced apomorphine supersensitivity in mice. J Neural Transm 68: 241–255

    PubMed  Google Scholar 

  • Marangos JM, Patel J, Miller C, Martino AM (1982) Specific calcium antagonist binding sites in brain. Life Sci 31: 1575–1585

    PubMed  Google Scholar 

  • Pileblad E, Carlsson A (1986) In vivo effects of the Ca2+ antagonist nimodipine on dopamine metabolism in mouse brain. J Neural Transm 66: 171–187

    PubMed  Google Scholar 

  • Pileblad E, Carlsson A (1987) The Ca++-antagonist nimodipine decreases and the Ca++ bay K 8644 increases catecholamine synthesis in mouse brain. Neuropharmacology 26: 101–105

    PubMed  Google Scholar 

  • Rossetti ZL, Mercuro G, Rivano AC (1983) A study of the factors affecting flow gradient analysis of catecholamines, DOPA and DOPAC by ion-pair liquid chromatography with electrochemical detection. Life Sci 33: 2387–2395

    PubMed  Google Scholar 

  • Shah AB, Poiletman M, Shah NS (1983) The influence of nisoldipine — a “calcium entry blocker” on drug induced stereotyped behavior in rats. Prog Neuropsychopharmacol Biol Psychiatr 7: 165–173

    Google Scholar 

  • Yamauchi T, Fujisawa H (1980) Involvement of calmodulin in the Ca2+-dependent activation of rat brainstem tyrosine 3-monooxygenase. Biochem Int 1: 98–104

    Google Scholar 

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Fadda, F., Gessa, G.L., Mosca, E. et al. Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain. J. Neural Transmission 75, 195–200 (1989). https://doi.org/10.1007/BF01258630

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  • DOI: https://doi.org/10.1007/BF01258630

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