Skip to main content
SpringerLink
Log in

In vivo effects of the Ca2+-antagonist nimodipine on dopamine metabolism in mouse brain

  • Original Papers
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

The effects of the Ca2+-antagonist nimodipine on central dopamine (DA) neurons in mice were investigatedin vivo. Nimodipine caused a dose-dependent decrease in the DA metabolite 3-methoxytyramine (3-MT) in striatum and the limbic region. If the brains were microwave radiated immediately after decapitation in order to minimize post-mortal accumulation of 3-MT, the effect of nimodipine was less pronounced and statistically not significant.

Nimodipine markedly decreased the accumulation of 3-MT induced by pargyline, an inhibitor of monoamine oxidase, a phenomenon that was not attenuated by microwave radiation. Furthermore, whereas nimodipine had no effect on mouse motor activity when given alone it readily blocked the pargyline-induced increase in activity.

The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum and the limbic region were also reduced by nimodipine as was the accumulation of 3,4-dihydroxyphenylalanine (DOPA) measured after inhibition of the aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015). In addition, nimodipine caused decreased concentrations of DA and homovanillic acid (HVA) in the limbic region but not in striatum.

Nimodipine caused an increase in the striatal concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); these changes were not seen in the limbic region.

In conclusion, nimodipine appears to reduce the release as well as the synthesis of DA in mouse brain. These effects are believed to be related to the Ca2+-antagonism of nimodipine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DPJ, Hundley MB, Johnsson RK, Strom JA, Transou CR (1983) Cerebral arterial spasm — a controlled trial of nimodipine in patients with subarachnoid hemorrhage. New Engl J Med 308: 619–624

    PubMed  Google Scholar 

  • Carlsson A, Davis JN, Kehr W, Lindqvist M, Atack CV (1972) Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brainin vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedebergs Arch Pharmacol 275: 153–168

    PubMed  Google Scholar 

  • Carlsson A, Lindqvist M (1973)In-vivo measurements of tryptophan and tyrosine hydroxylase activities in mouse brain. J Neural Transm 34: 79–91

    PubMed  Google Scholar 

  • Carlsson A, Lindqvist M, Kehr W (1974) Postmortal accumulation of 3-methoxytyramine in brain. Naunyn-Schmiedebergs Arch Pharmacol 284: 365–372

    PubMed  Google Scholar 

  • Carlsson L, Abrahamsson T, Almgren O (1985) Local release of myocardial norepinephrine during acute ischemia: An experimental study in the isolated perfused rat heart. J Cardiovasc Pharmacol 7: 791–798

    PubMed  Google Scholar 

  • Cena V, Nicolas GP, Sanchez-Garcia P, Kirpekar SM, Garcia AG (1983) Pharmacological dissection of receptor-associated and voltage-sensitive ionic channels involved in catecholamine release. Neuroscience 10: 1455–1462

    PubMed  Google Scholar 

  • El Mestikawy S, Glowinski J, Hamon M (1983) Tyrosine hydroxylase activation in depolarized dopaminergic terminals — involvement of Ca2+-dependent phosphorylation. Nature 302: 830–832

    PubMed  Google Scholar 

  • Felice LJ, Felice JD, Kissinger PT (1978) Determination of catecholamines in rat brain parts by reversed-phase ion-pair liquid chromatography. J Neurochem 31: 1461–1465

    PubMed  Google Scholar 

  • Fleckenstein A (1983) History of calcium antagonists. Circ Res 52 [Suppl] 1: 3–16

    Google Scholar 

  • Gelmers HJ (1983) Nimodipine, a new calcium antagonist in the prophylactic treatment of migraine. Headache 23: 106–109

    PubMed  Google Scholar 

  • Gelmers HJ (1984) The effects of nimodipine on the clinical course of patients with acute ischemic stroke. Acta Neurol Scand 69: 232–239

    PubMed  Google Scholar 

  • Glossmann H, Ferry DR, Lübbecke F, Mewes R, Hofmann F (1982) Calcium channels: Direct identification with radioligand binding studies. Trends Pharmacol Sci 3: 431–437

    Google Scholar 

  • Godfraind T, Miller RC (1983) Specificity of action of Ca++ entry blockers: A comparison of their actions in rat arteries and in human coronary arteries. Circ Res 52: 81–91

    Google Scholar 

  • Harris JE, Roth RH (1971) Potassium-induced acceleration of catecholamine biosynthesis in brain slices: A study on the mechanism of action. Mol Pharmacol 7: 593–604

    PubMed  Google Scholar 

  • Hirata Y, Nagatsu T (1985) Evidence for the involvement of Ca2+-calmodulin and cyclic AMP in the regulation of the tyrosine hydroxylase system in rat striatal tissue slices. Biochem Pharmacol 34: 2637–2643

    PubMed  Google Scholar 

  • Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioural effects of nimodipine in animals. Arzneim Forsch 32: 347–360

    Google Scholar 

  • Kazda S, Garhoff B, Krause HP, Schlossman K (1982) Cerebrovascular effects of the calcium antagonistic dihydropyridine derivate nimodipine in animal experiments. Arzneim Forsch 32: 331–338

    Google Scholar 

  • Kazda S, Towart R (1982) Nimodipine: a new calcium antagonistic drug with a preferential cerebrovascular action. Acta Neurochir 63: 259–265

    Google Scholar 

  • Kehr W (1976) 3-Methoxytyramine as an indicator of impulse-induced dopamine release in rat brainin vivo. Naunyn-Schmiedebergs Arch Pharmacol 293: 209–215

    PubMed  Google Scholar 

  • Ljunggren B, Brandt L, Säveland H, Nilsson P-E, Cronqvist S, Andersson K-E, Vinge E (1984) Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 61: 864–873

    PubMed  Google Scholar 

  • Magnusson O, Nilsson LB, Westerlund D (1980) Simultaneous determination of dopamine, dopac and homovanillic acid. Direct injection of supernatants from brain tissue homogenates in a liquid chromatography-electrochemical detection system. J Chromatogr 221: 237–247

    PubMed  Google Scholar 

  • Meyer JS, Hardenberg J (1983) Clinical effectivness of calcium entry blockers in prophylactic treatment of migraine and cluster headaches. Headache 23: 266–277

    PubMed  Google Scholar 

  • Middlemiss DN, Spedding M (1985) A functional correlate for the dihydropyridine binding sites in rat brain. Nature 314: 94–96

    PubMed  Google Scholar 

  • Miller RJ, Freedman SB (1984) Are dihydropyridine binding sites voltage sensitive calcium channels? Life Sci 34: 1205–1221

    PubMed  Google Scholar 

  • Nayler WG, Sturrock WJ (1983) An inhibitory effect of verapamil and diltiazem on the release of noradrenaline from ischemic and reperfused hearts. J Mol Cell Cardiol 16: 331–344

    Google Scholar 

  • Nayler WG, Sturrock WJ (1985) Inhibitory effect of calcium antagonists on the depletion of cardiac norepinephrine during postischemic reperfusion. J Cardiovasc Pharmacol 7: 581–587

    PubMed  Google Scholar 

  • Nordström Ö, Braesh-Andersen S, Bartfai T (1986) Dopamine release is enhanced while acetylcholine release is inhibited by nimodipine (Bay e 9736). Acta Physiol Scand 126: 115–119

    PubMed  Google Scholar 

  • Porter LD, Gardiner LM, de Belleroche J (1985) Nimodipine has an inhibitory action on neurotransmitter release from human cerebral arteries. J Cereb Blood Flow Metabol 5: 338–342

    Google Scholar 

  • Raemsch K-D, Graefe K-H, Sommer J (1985) Pharmacokinetics and metabolism of nimodipine. In: Betz E, Deck K, Hoffmeister F (eds) Nimodipine — pharmacological and clinical properties. Proceedings of the 1st internat Nimotop-symposium, Munich, 1984. KF Schattauer, Stuttgart New York, pp 148–161

    Google Scholar 

  • Schramm M, Thomas G, Towart R, Franckowiak G (1983) Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature 314: 94–96

    Google Scholar 

  • Scriabine A, Battye R, Hoffmeister F, Kazda S, Towart R, Garhoff B, Schluter G, Raemsch K-D, Scherling D (1985) Nimodipine. In: Scriabine A (ed) New cardiovascular drugs. New York: Raven Press, pp 197–218

    Google Scholar 

  • Simon JR, Roth RH (1979) Striatal tyrosine hydroxylase: Comparison of the activation produced by depolarization and dibutyryl-cAMP. Mol Pharmacol 16: 224–233

    PubMed  Google Scholar 

  • Spedding M (1985) Calcium antagonist subgroups. Trends Pharmacol Sci 6: 109–114

    Google Scholar 

  • Steen PA, Newberg LA, Milde JH, Michenfelder JD (1984) Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog. J Cerebr Blood Flow Metab 4: 82–87

    Google Scholar 

  • Takahashi M, Ogura A (1983) Dihydropyridines as potent calcium channel blockers in neuronal channels. FEBS Lett 152: 191–195

    PubMed  Google Scholar 

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

    Google Scholar 

Download references

Author information

Author notes

  1. E. Pileblad

    Present address: Department of Pharmacology, University of Göteborg, Göteborg, Sweden

Authors and Affiliations

  1. Department of Pharmacology, University of Göteborg, Göteborg, Sweden

    A. Carlsson

Authors
  1. E. Pileblad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Carlsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pileblad, E., Carlsson, A. In vivo effects of the Ca2+-antagonist nimodipine on dopamine metabolism in mouse brain. J. Neural Transmission 66, 171–187 (1986). https://doi.org/10.1007/BF01260912

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01260912

Key words

Search

Navigation