Antihypertensive effects of lercanidipine in experimental hypertensive rats and dogs.
The antihypertensive action of lercanidipine (CAS 132866-11-6, Rec 15/2375), a new 1,4-dihydropyridine (1,4-DHP) calcium entry blocker (CEB), was examined in spontaneously hypertensive rats (SHR) and renal hypertensive dogs after acute and repeated administration, in comparison to several reference 1,4-DHPs. In acute experiments in SHR, lercanidipine reduced diastolic blood pressure showing a potency similar to felodipine and 2-3 fold higher than those of nicardipine and nitrendipine, after both intravenous and oral administration. Analysis of the area under the curves of percent reduction of diastolic blood pressure exerted for 3 and 8 h after intravenous and oral administrations, respectively, showed that the duration of the antihypertensive effect of lercanidipine was longer than that of the reference dihydropyridines. After repeated administrations to SHR no tachyphylaxis was observed, as indicated by the marked and persistent decrease in systolic blood pressure elicited by lercanidipine, given orally once a day for 21 days. Moreover, starting from the first week of treatment, the daily basal values of systolic blood pressure of the rats treated with lercanidipine were significantly lower than those of the placebo-treated group. In renal hypertensive dogs, after acute oral administration, lercanidipine was as potent as nitrendipine. After repeated administration, the action of lercanidipine was longer lasting than that of nicardipine and no decrease in the antihypertensive effects was observed. The in vivo studies show that lercanidipine has a potent and long-lasting antihypertensive profile, suggesting that this compound may be used for once-a-day treatment.
Sironi
G
G
Research and Development Division, Recordati S.p.A., Milan, Italy.
Montagna
E
E
Greto
L
L
Bianchi
G
G
Leonardi
A
A
Testa
R
R
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002404:Catheterization; D004095:Dihydropyridines / Q000627:therapeutic use*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060343:lercanidipine