Drugs online research references
Methods Find Exp Clin Pharmacol. 1994 Nov;16(9):633-8.
Long-lasting ex vivo inhibition by perindopril of rat vascular response to angiotensin I.
Ishigai Y, Fukuzawa A, Chiba K, Irie K, Shibano T.
Exploratory Research Laboratories II, Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd., Japan.
The ex vivo effects of perindopril and enalapril, inhibitors of angiotensin-converting enzyme (ACE), were studied on rat aortae and perfused hearts to clarify the inhibition of vascular response to angiotensin I. The duration of the effects of these inhibitors was also studied. One hour after oral administration of perindopril (0.1-30 mg/kg) or enalapril (0.3-100 mg/kg), the aortae and hearts were isolated for the measurement of isometric force and coronary flow, respectively. In aortae, perindopril and enalapril dose-dependently inhibited the maximal contractions to angiotensin I (1-1000 nM). In isolated perfused hearts, the compounds inhibited the decrease in coronary flow induced by angiotensin I (100 ng). In other experiments, the inhibitory effects of perindopril lasted for 24 h in both aortae (3 mg/kg, p.o.) and hearts (10 mg/kg, p.o.). In contrast, the effects of enalapril disappeared within 6 h in aortae (3 mg/kg, p.o.) and 12 h in hearts (100 mg/kg, p.o.). These results demonstrate that oral administration of ACE inhibitors reduce the ex vivo vascular response to angiotensin I and suggest that perindopril is a longer-lasting inhibitor than enalapril on vascular contraction to locally generated angiotensin II.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7746024&dopt=Abstract
Adv Exp Med Biol. 1986;198 Pt A:411-7.
Carboxyalkyl peptide inhibitors of kininase II: chiral synthesis.
Chung AY, Ryan JW.
Heretofore, carboxyalkyl peptide inhibitors of kininase II (e.g. N-[1-carboxy-3-phenylpropyl]-Ala-Pro, "enalaprilic acid") have been synthesized by means that yield racemic product. Typically, the secondary amine bond is formed by reacting an amino acid or dipeptide with a 2-keto carboxylic acid ester or imide. The group providing the 2-keto function must be used in excess, and the desired S,S,S isomer must be obtained by resolution procedures. We have developed a procedure whereby enalaprilic acid, RAC-X-64 and related compounds are synthesized stereospecifically and in relatively high yields.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3028059&dopt=Abstract
Peptides. 1994;15(8):1445-9.
Effects of peptidase inhibitors on bradykinin-induced bronchoconstriction in the rat.
Schilero GJ, Almenoff P, Cardozo C, Lesser M.
Department of Medicine, Mount Sinai School of Medicine, New York, NY.
Objectives of this study were to determine if aerosolized bradykinin causes bronchoconstriction in anesthetized, mechanically ventilated rats, and if pretreatment with enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), or phosphoramidon, an inhibitor of endopeptidase 24.11 (EP 24.11), alters the response. We found that aerosolized bradykinin elicited a reproducible bronchoconstrictor response that was significantly amplified by pretreatment with aerosolized enalaprilat or phosphoramidon. Neither inhibitor alone affected airway tone or caused nonspecific airway hyperreactivity. These findings indicate that both ACE and EP 24.11 contribute to bradykinin degradation in rat airways.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7700846&dopt=Abstract
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