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Effects of butyrophenones on the sympathetic nerves of the isolated rabbit heart and on the postsynaptic α-adrenoceptors of the isolated rabbit aorta

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Summary

In isolated rabbit hearts perfused with Tyrode solution we studied the effects of droperidol, haloperidol, and trifluperidol on the noradrenaline uptake into, and release from, the terminal sympathetic nerves. The noradrenaline in the perfusate was measured spectrofluorimetrically. The effects of the butyrophenones on the postsynaptic α-adrenoceptors were determined in isolated aortic strips of rabbits, and the possibility that dopamine receptor agonists may relax rabbit aortic smooth muscle was examined in strips contracted with 25 mM KCl. Alterations in tension induced by the drugs were measured.

  1. 1.

    The uptake of exogenous noradrenaline from the perfusion fluid into the sympathetic nerves was inhibited by the butyrophenones.

  2. 2.

    Droperidol, haloperidol, and trifluperidol did not alter the spontaneous noradrenaline release. The noradrenaline release in response to electrical stimulation of the postganglionic sympathetic nerves was enhanced at droperidol concentrations of 4.2×10−6 and 1.3×10−5 M. At higher concentrations the electrically stimulated output of noradrenaline was decreased.

  3. 3.

    Perfusion of rabbit hearts with cocaine throughout the experiments abolished the increase in electrically stimulated noradrenaline output caused by 4.2×10−6 and 1.3×10−5 M droperidol. In rabbit hearts perfused with 1.3×10−5 M droperidol throughout the experiments, cocaine did not increase the noradrenaline output evoked by electrical nerve stimulation.

  4. 4.

    Droperidol (1.3×10−5 M) failed to antagonize the decrease in electrically stimulated noradrenaline output induced by oxymetazoline.

  5. 5.

    The noradrenaline output evoked by 80 mM KCl was inhibited by the butyrophenones. A correlation exists between the inhibitory potencies of the drugs and their octanol/water partition coefficients.

  6. 6.

    The butyrophenones also decreased the noradrenaline output induced by activation of the nicotinic receptors on the terminal sympathetic nerves by acetylcholine in the presence of atropine.

  7. 7.

    Apomorphine did not affect the noradrenaline output and the increase in heart rate evoked by electrical stimulation of the postganglionic sympathetic nerves at frequencies of 2.5 and 5 Hz.

  8. 8.

    The concentration-response curves of various α-adrenoceptor agonists for their increasing effect on tension of rabbit aortic strips were shifted to the right in a parallel fashion by the butyrophenones.

  9. 9.

    Apomorphine and dopamine failed to relax aortic strips contracted with KCl.

It is concluded that the inhibition of neuronal uptake of noradrenaline by droperidol accounts for the increase in electrically stimulated overflow of noradrenaline. The butyrophenones which are potent inhibitors of the postsynaptic α-adrenoceptors failed to block the presynaptic α-adrenoceptors on the terminal sympathetic nerves. Dopamine receptors could not be detected presynaptically on the cardiac sympathetic nerves nor postsynaptically in the aortic smooth muscle.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Hamburg, Martinistrasse 52, D-2000, Hamburg 20, Germany

    M. Göthert, H. -J. Lox & J. -M. Rieckesmann

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Göthert, M., Lox, H.J. & Rieckesmann, J.M. Effects of butyrophenones on the sympathetic nerves of the isolated rabbit heart and on the postsynaptic α-adrenoceptors of the isolated rabbit aorta. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 255–265 (1977). https://doi.org/10.1007/BF00500968

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