+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Cardiovascular effects and interaction with adrenoceptors of urapidil

Cardiovascular effects and interaction with adrenoceptors of urapidil

Archives Internationales de Pharmacodynamie et de Therapie 276(2): 180-201

Urapidil is a novel antihypertensive agent, chemically related to uracil. Its cardiovascular profile was evaluated in a variety of pharmacological models. Urapidil caused a significant decrease of blood pressure in intact rats, both hypertensive (SHR) and normotensive (WKY), as well as in .alpha.-glucochloralose-anaesthetized cats. Reflex tachycardia was not observed. An analysis in pithed rats showed that urapidil is an .alpha.-andrenoceptor blocking drug with an obvious selectivity for postsynaptic .alpha.1-over .alpha.2-adrenoceptors. The .alpha.1-adrenoceptor blocking potency proved quantitatively less than that of prazosin. Experiments on isolated aorta preparations and radioligand binding studies confirmed the selectivity of urapidil for .alpha.1-over .alpha.2-adrenoceptors. The involvement of urapidil with prysynaptic .alpha.2-adrenoceptors proved neglible. Urapidil proved to possess modest but significant .beta.2-adrenoceptor blocking activity, accompanied by a certain degree of intrinsic sympathomimetic activity (TSA) at the level of the cardiac .beta.1-adrenoceptors. No significant interaction with vascular .beta.2-adrenoceptors was observed. High doses of urapidil caused pressor effects of a probably unspecific nature; neither .alpha.-adrenoceptors nor 5HT-receptors were involved. When injected into the vertebral artery of the cat, urapidil caused a significant central hypotensive effect which was different from that of clonidine and related drugs, since it could not be blocked by yohimbine (.alpha.2-receptor antagonist). Similarly, the modest sedation produced by urapidil in mice remained uninfluenced by yohimbine. The urapidil molecule does not contain any stereoisomers. Accordingly, one and the same molecule possesses the following pharmacodynamic properties: postsynaptic .alpha.1-adrenoceptor blockade; weak postsynapic .alpha.2-adrenoceptor blockade; modest but selective .beta.1-adrenoceptor blockade with ISA; central hypotensive activity not mediated by central .alpha.2-adrenoceptors.

(PDF emailed within 1 workday: $29.90)

Accession: 004883442

Download citation: RISBibTeXText

PMID: 4051641

Related references

Interaction of the antihypertensive drug urapidil with cardiac beta-adrenoceptors in vitro. European Journal of Pharmacology 104(1-2): 169-172, 1984

Interaction of 5-methyl-urapidil with alpha 1-adrenoceptors in canine blood vessels: impact of pacing-induced heart failure. European Journal of Pharmacology 318(1): 55-63, 1996

The effect of urapidil on cardiac alpha adrenoceptors and beta adrenoceptors. Arzneimittel Forschung 36(10): 1471-1476, 1986

Effects of urapidil on blood pressure and adrenoceptors in various animal models. Journal of Hypertension. Supplement 2(3): S539-S541, 1984

In vivo effects on beta adrenoceptors of the alpha adrenoceptor antagonist urapidil. Naunyn Schmiedeberg'S Archives Of Pharmacologyuppl: R79, 1985

Relative presynaptic and postsynaptic effects of urapidil on adrenoceptors in the rabbit pulmonary artery. Journal of Pharmacology and Experimental Therapeutics 237(3): 746-749, 1986

Comparison of effects of urapidil prazosin and clonidine on alpha adrenoceptors in isolated organ preparations. Folia Pharmacologica Japonica 84(5): 124P, 138P, 1984

Cardiovascular effects of urapidil. Journal de Pharmacologie 14(4): 465-472, 1983

Influence of blockade of a1-adrenoceptors, b1-adrenoceptors and vasopressin V1A receptors on the cardiovascular effects of 2-melanocyte-stimulating hormone (2-MSH). Naunyn-Schmiedeberg's Archives of Pharmacology 355(6): 720-726, 1997

Effects of urapidil on the cardiovascular response to intratracheal intubation. Annales Francaises D'anesthesie et de Reanimation 10(2): 113-116, 1991

Ketanserin versus urapidil: Age-related cardiovascular effects in conscious rats. European Journal of Pharmacology 435(1): 85-92, 18 January, 2002

Interaction with histamine H1-receptors and bronchospasmolytic effects of urapidil. Respiration; International Review of Thoracic Diseases 51(1): 16-25, 1987

Effect of urapidil on beta-adrenoceptors of rat atria. European Journal of Pharmacology 108(2): 193-196, 1985

Effects of urapidil on cardiovascular response to tracheal intubation and incision during fentanyl co-induction. Hunan Yi Ke Da Xue Xue Bao 25(4): 382-384, 2002

Influence of blockade of alpha 1-adrenoceptors, beta 1-adrenoceptors and vasopressin V1A receptors on the cardiovascular effects of gamma 2-melanocyte-stimulating hormone (gamma 2-MSH). Naunyn-Schmiedeberg's Archives of Pharmacology 355(6): 720-726, 1997