Abstract |
The pharmacological properties of a novel vasodilator/ beta-adrenoceptor antagonist, SK & F 95018 6-[4-[3-(3-[4-(2-Cyclopropylmethoxyethyl)phenoxy]-2- hydroxypropylamino)propionamido]phenyl]-4,5-dihydro-5-met hylpyridazin- 3(2H)-one methanesulphonate] are described. SK & F 95018 lowered blood pressure and increased hindquarters blood flow in anaesthetised rats over the same dose range 1-5 mumol kg-1. Over a similar dose range SK & F 95018 inhibited isoprenaline-induced tachycardia in ganglion-blocked, anaesthetized cats. SK & F 95018 had minimal effect on bronchial beta 2-adrenoceptors, while simultaneously antagonizing cardiac beta 1-adrenoceptors in anaesthetized guinea-pigs. SK & F 95018 was demonstrated to be a potent antihypertensive agent in conscious spontaneously hypertensive rats over the dose range of 1.6-13 mumol kg-1 i.v. and 13-103 mumol kg-1 p.o. A marked and persistent hypotension was observed in conscious cats at a dose of 7.5 mumol kg-1 i.v. and 19 mumol kg-1 p.o., without reflex tachycardia. In anaesthetized cats, the hypotensive response to the compound was found to be via a reduction in total peripheral resistance with a maintained cardiac output. Vasodilatation and beta- adrenoceptor antagonism have been demonstrated in the same molecule ( SK & F 95018) in a combination which would be suitable for effective treatment of hypertension.
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Authors | G T Swayne, D A Owen, E M Taylor, R J Eden, R A Slater, W Howson |
Journal | Archives internationales de pharmacodynamie et de therapie
(Arch Int Pharmacodyn Ther)
Vol. 289
Issue 2
Pg. 251-66
(Oct 1987)
ISSN: 0003-9780 [Print] Belgium |
PMID | 2892473
(Publication Type: Journal Article)
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Chemical References |
- Adrenergic beta-Antagonists
- Antihypertensive Agents
- Phosphodiesterase Inhibitors
- Pyridazines
- SK&F 95018
- Vasodilator Agents
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Topics |
- Adrenergic beta-Antagonists
- Animals
- Antihypertensive Agents
- Cats
- Dose-Response Relationship, Drug
- Female
- Heart Rate
(drug effects)
- Hindlimb
(blood supply)
- In Vitro Techniques
- Male
- Perfusion
- Phosphodiesterase Inhibitors
- Pyridazines
(pharmacology)
- Rats
- Rats, Inbred Strains
- Regional Blood Flow
(drug effects)
- Vasodilator Agents
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