NS-49, an alpha 1A-adrenoceptor agonist, selectively increases intraurethral pressure in dogs.

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Taniguchi N, Hamada K, Ogasawara T, Ukai Y, Yoshikuni Y, Kimura K

NS-49, an alpha 1A-adrenoceptor agonist, selectively increases intraurethral pressure in dogs.

Eur J Pharmacol. 1996 Dec 27;318(1):117-22.

PubMed ID

9007522 [ View in PubMed

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Abstract

The effects of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane sulfonanilide hydrochloride), an alpha 1A-adrenoceptor-selective agonist, on intraurethral pressure and blood pressure were investigated in anesthetized dogs. In addition, the contractile effects of NS-49 on the isolated dog urethra and carotid artery were compared with those of non-selective alpha 1-adrenoceptor agonists. Intravenously (i.v.) administered NS-49 at 0.3 microgram/kg or more significantly increased intraurethral pressure in a dose-dependent manner. Much higher doses of NS-49 were needed to increase blood pressure. In contrast, ST-1059 (1-(2',5'-dimethoxyphenyl)-2-aminoethanol) (an active metabolite of midodrine) at 30 micrograms/kg or more significantly increased both intraurethral pressure and blood pressure. NS-49 was 11-fold more selective for intraurethral pressure than ST-1059, NS-49, ST-1059, phenylephrine and noradrenaline caused concentration-dependent contraction of the isolated dog urethra. NS-49 caused only a slight contraction of the dog carotid artery even at high concentrations, whereas the reference drugs caused contractions of the artery with high efficacy. The alpha 1A-adrenoceptor-selective antagonists 5-methyl-urapidil and WB-4101 also showed high affinity for alpha 1-adrenoceptors in the dog urethra in inhibiting [3H]prazosin binding. In conclusion, the alpha 1A-selective agonist NS-49 selectively increased intraurethral pressure in dogs, and produced selective contraction of the dog urethra. These results suggest that the alpha 1A-adrenoceptor subtype is responsible for the contraction of the urethra and the regulation of intraurethral pressure, and that NS-49 might be useful for the treatment of stress incontinence with little effect on the cardiovascular system.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Midodrine	Alpha-1A adrenergic receptor	Protein	Humans	Yes	Agonist	Details