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  • Title: Importance of central nervous system serotonin-1A receptors for mediating the hypotensive effect of urapidil.
    Author: Mandal AK, Kellar KJ, Friedman E, Pineo SV, Hamosh P, Gillis RA.
    Journal: J Pharmacol Exp Ther; 1989 Nov; 251(2):563-70. PubMed ID: 2530339.
    Abstract:
    Urapidil is thought to lower blood pressure by both a peripheral and a central mechanism. The former effect is caused by blockade of alpha-1 adrenoceptors whereas the latter effect has been shown to occur in the medulla, specifically at the intermediate area on the ventral surface of the medulla. The receptor mediating the central effect is not the alpha-1 adrenoceptor, but has been postulated to be the serotonin (5-HT)1A receptor. To determine whether urapidil lowers blood pressure by stimulating 5-HT1A receptors at the intermediate area, we applied urapidil bilaterally (50 micrograms/side) to the intermediate area of chloralose-anesthetized cats while monitoring arterial blood pressure and heart rate. Application of urapidil caused decreases in mean blood pressure and heart rate of 66 +/- 8 mm Hg and 31 +/- 7 beats/min, respectively. Pretreatment with the 5-HT1A and 5-HT2 receptor antagonist, spiperone (30 micrograms/side), counteracted the effects of urapidil. Pretreatment with the 5-HT2 receptor antagonist, ketanserin, did not alter the hypotensive effect of urapidil. Urapidil given i.v. in a dose of 2 mg/kg decreased mean blood pressure and heart rate by 53 +/- 6 mm Hg and 10 +/- 2 beats/min, respectively. At the peak of the i.v. response, spiperone (30 micrograms/side) was applied to the intermediate area and increased mean blood pressure and heart rate by 52 +/- 6 mm Hg and 20 +/- 4 beats/min, respectively, thus effectively reversing the effects of i.v. urapidil.(ABSTRACT TRUNCATED AT 250 WORDS)
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