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Involvement of presynaptic alpha-adrenoceptors in the cardiovascular and sedative effects of FLA-136

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Summary

  1. 1.

    The effects of FLA-136 [4-amino-3-(2,6-dichlorobenzylidenehydrazino)-1,2,4-triazol] on blood pressure and heart rate in anaesthetized, normotensive rats, stimulation-induced tachycardia in pithed rats and sedation in mice were studied.

  2. 2.

    Following intravenous administration to anaesthetized normotensive rats FLA-136 caused a dose-dependent decrease in mean arterial pressure accompanied by a reduction in cardiac frequency. Both actions showed a slow onset and maximal effects were reached about 1 h after application. Yohimbine and piperoxan almost completely inhibited these haemodynamic effects of FLA-136, whereas prazosin was ineffective. The efficacy of FLA-136 in reducing blood pressure and heart rate was partly impaired after pretreatment with reserpine (5 mg/kg), and totally abolished in animals which had received this reserpine treatment twice and α-methyl-p-tyrosine methylester.

  3. 3.

    FLA-136 neither displayed an acute effect on the stimulation-induced tachycardia nor affected the clonidine-induced reduction of the elevated heart rate in pithed rats. In contrast, the cardiac, responses to stimulation were dose-dependently diminished after pretreatment with FLA-136. At high doses FLA-136 moderately decreased the hypertensive effect of clonidine.

  4. 4.

    FLA-136 dose-dependently prolonged the hexobarbitone (75 mg/kg) induced loss of the righting reflex in mice. This action of FLA-136 was antagonized by previous pretreatment with yohimbine and piperoxan, whereas mianserin was less effective. Prazosin tended to increase the sedative effect of FLA-136.

  5. 5.

    The results suggest the involvement of presynaptic α-adrenoceptors in the cardiovascular and sedative properties of FLA-136. These effects, however, may not be caused by FLA-136 itself, but are possibly mediated by one more active metabolites.

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Authors and Affiliations

  1. Department of Pharmacy, Division of Pharmacotherapy, University of Amsterdam, Plantage Muidergracht 24, Amsterdam, The Netherlands

    P. B. M. W. M. Timmermans, E. Lam & P. A. van Zwieten

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  1. P. B. M. W. M. Timmermans
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  2. E. Lam
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  3. P. A. van Zwieten
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Timmermans, P.B.M.W.M., Lam, E. & van Zwieten, P.A. Involvement of presynaptic alpha-adrenoceptors in the cardiovascular and sedative effects of FLA-136. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 127–134 (1979). https://doi.org/10.1007/BF00498982

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  • DOI: https://doi.org/10.1007/BF00498982

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