ANTIHYPERTENSIVE ACTIVITY OF DL-15-DEOXY-16-HYDROXY-16(ALPHA/BETA)-VINYL PROSTAGLANDIN-E2 METHYL-ESTER (CL-115,347), A NEW ORALLY AND TRANSDERMALLY LONG-ACTING ANTIHYPERTENSIVE AGENT

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (3) , 726-732
Abstract
CL 115,347 [dl-15-deoxy-16-hydroxy-16(.alpha./.beta.)-vinyl prostaglandin E2 methyl ester] has a broad spectrum in antihypertensive activity in many animal hypertension models in every species tested. In conscious spontaneously hypertensive rats, CL 115,347 at 0.25 to 10 mg/kg orally produced 31-53 mm Hg lowering of the mean arterial blood pressure (MABP) with a duration of action of 1 to > 8 h. When applied transdermally, CL 115,347 was more potent and longer acting than by the oral route. At 0.03-1 mg/kg, topically applied CL 115,347 lowered MABP of spontaneously hypertensive rats 27 to 46 mm Hg. Duration of action was > 6 to > 24 h. CL 115,347 was also active in conscious normotensive rats (-27 mm Hg), deoxycorticosterone-salt-induced hypertensive rats (-51 mm Hg) and aorta-coarcted hypertensive rats (-52 mm Hg) when tested at 1 mg/kg orally. At 3 mg/kg orally, CL 115,347 lowered MABP of Dahl S salt-sensitive rats 55 mm Hg. CL 115,347 orally and s.c. lowered MABP in 2 kidney, 1 clip Goldblatt renal hypertensive dogs and was accompanied by tachycardia. CL 115,347, at 0.1 and 0.2 mg/kg orally, maximally lowered the systolic blood pressure of conscious rhesus monkey [Macaca mulatta] 33-63 mm Hg with only a slight increase in heart rate. CL 115,347 was antihypertensive in animals with low, normal and high plasma renin activity. CL 115,347 may be useful for the treatment of human hypertension.

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