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R 28935 and prazosin: Effects on central and peripheral alpha-adrenoreceptor activity and on blood pressure

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Summary

  1. 1.

    The effects of erythro-1-{1-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-4-piperidyl}-2-benzimidazolinone (R 28935), prazosin and phenoxybenzamine on the clonidine-induced increases in the flexor relfex activity and in the blood pressure of rats were used to study their influence on postsynaptic α-adreno-receptors centrally and peripherally, respectively. R 28935 was more potent in blocking the central than the peripheral α-adrenoreceptors whereas the two receptor types were inhibited to about the same degree following prazosin and phenoxybenzamine.

  2. 2.

    The amphetamine-induced rotation of rats with unilateral inactivation of the corpus striatum and the apomorphine-induced stimulation of the motor activity of mice were inhibited by R 28935, but not by prazosin, indicating that R 28935 can block postsynaptic dopaminergic receptors.

  3. 3.

    The α-methyltyrosine-induced disappearance of noradrenaline in the brain and the spinal cord of rats was only slightly accelerated by prazosin but was more effectively accelerated by R 28935 and phenoxybenzamine. The deceleration by clonidine of the α-methyltyrosine-induced disappearance of noradrenaline was partially inhibited by R 28935 but was not influenced by prazosin indicating that central α-autoreceptors (presynaptic α-receptors) are only weakly blocked by R 28935 and not at all blocked by prazosin.

  4. 4.

    The blood pressure of intact rats was lowered by prazosin and phenoxybenzamine at doses effectively blocking vascular α-adrenoreceptors. On the other hand, R 28935 caused hypotension at doses blocking central but not peripheral α-adrenoreceptors suggesting that the hypotension might be due to inhibition of central noradrenergic neurotransmission.

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Author notes

  1. Cecilia Gomes

    Present address: Department of Biochemistry and Pharmacology, Escola Paulista de Medicina, S. Paulo, Brazil

Authors and Affiliations

  1. Department of Pharmacology, University of Göteborg, Fack, S-400 33, Göteborg, Sweden

    Nils-Erik Andén, Cecilia Gomes, Bengt Persson & Gustaf Trolin

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  1. Nils-Erik Andén
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  2. Cecilia Gomes
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  3. Bengt Persson
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  4. Gustaf Trolin
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Andén, NE., Gomes, C., Persson, B. et al. R 28935 and prazosin: Effects on central and peripheral alpha-adrenoreceptor activity and on blood pressure. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 299–306 (1978). https://doi.org/10.1007/BF00508299

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  • DOI: https://doi.org/10.1007/BF00508299

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