Diuretic activity of N'-disubstituted morpholinoguanidine analogs of U-37883A in rats and dogs.
Methods Find Exp Clin Pharmacol
; 17(4): 255-66, 1995 May.
Article
em En
| MEDLINE
| ID: mdl-7475512
ABSTRACT
U-37883A is a K+ sparing diuretic which selectively blocks openers of vascular ATP-sensitive K channels. Many N'-disubstituted morpholinoguanidine (N'-DMG) analogs of U-37883A were synthesized and tested for diuretic activity. In conscious rats, 10-100 mg/kg orally of the most active N'-DMGs increased urine volume (V) and Na+ excretion by up to 4-fold with little kaliuresis. The N'-DMGs U-37997A and U-38658A were less potent than standard diuretics, but did not induce the K+ loss seen with hydrochlorothiazide and furosemide or the K+ retention of amiloride and triamterene. In conscious dogs, 10 mg/kg i.v. of the N'-DMGs U-40389A and U-52090 increased V and Na+ excretion by over 7-fold with little kaliuresis. Despite their attractive diuresis, all of the N'-DMGs had narrow margins of safety. Reflecting their direct myocardial depressant action, in isolated rat hearts, bolus intracoronary U-37883A, U-18177A, and U-38658A (0.25-10 mumol) severely reduced the rate (-10 to -100%) and force (-9 to -100%) of contraction. These studies characterize the eukalemic diuretic activity of N'-DMG analogs of U-37883A, and demonstrate the marked cardiac depression characteristic of the morpholinoguanidine diuretic series.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adamantano
/
Morfolinas
/
Diuréticos
Limite:
Animals
Idioma:
En
Revista:
Methods Find Exp Clin Pharmacol
Ano de publicação:
1995
Tipo de documento:
Article