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  • Title: Interaction of urapidil with brain serotonin-1A receptors increases the blood pressure reduction due to peripheral alpha-adrenoceptor inhibition.
    Author: Sanders KH, Beller KD, Bischler P, Kolassa N.
    Journal: J Hypertens Suppl; 1988 Dec; 6(2):S65-8. PubMed ID: 2906703.
    Abstract:
    The alpha-adrenoceptor antagonist urapidil influences central cardiovascular regulation, and this effect is unrelated to alpha-adrenoceptors. Since urapidil has appreciable affinity and selectivity for serotonin-1A (5HT1A) receptors, the activity of urapidil at these sites may be relevant for the centrally mediated component of its antihypertensive action. The latter hypothesis was tested by analysing the influence of the 5HT1A receptor antagonist spiroxatrine on the hypotensive response to urapidil, in comparison with the influence on the hypotensive response to the 5HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin). Anaesthetized cats were thoracotomized and artificially ventilated. Blood pressure was monitored in the descending aorta, and the drugs were injected into the vertebral artery. Spiroxatrine (0.1-3.0 nmol/kg) shifted the cumulative dose response curve (blood pressure reduction) of urapidil (3-20 nmol/kg) and of 8-OH-DPAT (0.01-0.1 nmol/kg) to the right, suggesting competitive antagonism. The results support the hypothesis that the effects of urapidil on central cardiovascular regulation and at least part of the hypotensive effects are due to 5HT1A receptor stimulation.
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