Antihypertensive effect of some oxazolo[3,2-a]pyridines, thiazolo[3,2-a]pyridines and pyrido[2,1-b]oxazines in conscious spontaneously hypertensive rats.
The antihypertensive activity of eighteen 'oxazolo[3,2-a]pyridine, thiazolo[3,2-a]pyridine and pyrido[2,1-b]oxazine derivatives has been evaluated in conscious spontaneously hypertensive rats (SHRs), and compared with that of nifedipine, used as reference. At a dose of 50 mg kg-1 (i.p.) eleven compounds resulted in a significant reduction in mean arterial blood pressure; four of the eleven were particularly effective, resulting in significant hypotension more than 6 h after administration and an effect that was still apparent after 24 h. The hypotension induced by nifedipine gradually decreased, disappearing 6-8 h after administration. The long-lasting activity shown by these compounds is, in general, not accompanied by reflex tachycardia. Intraperitoneal administration of two oxazolo[3,2-a]pyridine derivatives and two pyrido[2,1-b]oxazine derivatives resulted in potent and long-lasting antihypertensive action in SHRs. Further studies on the mechanism of action of these derivatives might help the determination of better structure-activity correlations and the design, synthesis and evaluation of better antihypertensive agents.
Moran
A
A
Departmento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Spain.
Martín
E
E
Velasco
C
C
Martín
M L
ML
San Roman
L
L
Caballero
E
E
Puebla
P
P
Medarde
M
M
San Feliciano
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D012015:Reference Standards; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D010078:Oxazines; D011725:Pyridines; D009543:Nifedipine