Reference

Analysis of the chronotropic effects of azelnidipine in anesthetized dogs: a comparison with amlodipine and nifedipine

Analysis of the chronotropic effects of azelnidipine in anesthetized dogs: a comparison with amlodipine and nifedipine. Fujisawa, Michio; Yorikane, Ryosuke; Koike, Hiroyuki (Pharmacology and Molecular Biology Research Laboratories, Sankyo Co. Ltd., Japan). Japanese Pharmacology & Therapeutics, 31(7), 553-564 (Japanese) 2003 Raifu Saiensu Shuppan K.K. CODEN: JPTABU. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effects of azelnidipine, a new 1,4-dihydropyridine Ca2+ channel antagonist (CCB), on heart rate (HR) were investigated in comparison with those of amlodipine and nifedipine. To examine the direct, i.e. 88150-42-9 and 123524-52-7 are cas registry numbers. These chemicals are also mentioned in this article. intrinsic neg. chronotropic, action of CCBs, we perfused sino-atrial node artery under a const. pressure in open-chest anesthetized dogs. CCBs were injected into the sinus node artery via the nelaton tubing in the perfusion circuit. Nifedipine was the most potent among three CCBs in reducing HR. The HR-decreasing effect of azelnidipine (1-10 mg) was 5 times more potent than that of amlodipine. The effects of i.v. administration of CCBs on HR were next examd. in anesthetized dogs. The blood pressure (BP)-lowering effect of azelnidipine (0.03-1.0 mg/kg, i.v.) was long-lasting and its onset of action was very slow. The lower doses caused only a little increase in HR, probably because of slow onset of hypotension, and the higher doses of azelnidipine reduced HR. The BP-lowering effects of nifedipine and amlodipine were more rapid than that of azelnidipine and therefore both drugs consistently caused an increase in HR via baroreceptor reflex. In autonomically blocked dogs, pre-treated with atropine and propranolol, the reflex increase in HR following administration of the CCBs was abolished and the administration of higher doses of azelnidipine or amlodipine decreased HR. An anal. of the correlation between hypotension and HR changes in this prepn. revealed that azelnidipine produced the greatest redn. of HR among three drugs tested at the same degree of hypotension. In conclusion, compared to amlodipine, azelnidipine had a greater intrinsic neg. chronotropic action and much less baroreceptor reflex activation due to the gradual BP-lowering action. These characteristics seemed to be involved in the HR-decreasing effect of azelnidipine obsd. when i.v. administered to autonomically intact dogs. .

Solid dosage forms angiotensin II receptor antagonist and a calcium channel blocker

All Rights Reserved. Solid dosage forms angiotensin II receptor antagonist and a calcium channel blocker. Hamaura, Takeshi; Kanno, Mitsuru (Sankyo Company, Limited, Japan). PCT Int. Appl. WO 2007001067 A2 4 Jan 2007, 34pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IS, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization). CODEN: PIXXD2. APPLICATION: WO 2006-JP313176 26 Jun 2006. PRIORITY: JP 2005-187214 27 Jun 2005. DOCUMENT TYPE: Patent CA Section: 63 (Pharmaceuticals) The invention relates to a solid dosage form comprising an angiotensin II receptor antagonist and a calcium channel blocker, wherein the active ingredients are formulated such that they are not intimately mixed in the solid dosage form. The solid dosage form demonstrates improved dissoln. 123524-52-7 and 9004-34-6 which are cas registry numbers of chemicals are mentioned. properties. Granules contained olmesartan medoxomil 10, lactose 76.6, low substituted, hydroxypropyl cellulose 20, hydroxypropyl cellulose 2.5, microcryst. cellulose 10, and Mg stearate 0.8 mg/tablet. .