Calcium entry blocking activities of MPC-1304 and of its enantiomers and metabolites

Okumura, Keiichi; Ichihara, Kenji; Nagasaka, Mitsuaki; Oda, Noriichi; Tajima, Kiyotaka

doi:10.1016/0014-2999(93)90821-x

Cited by 15 publications

(4 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To elucidate whether the spasmolytic effect of the extract is also mediated through the Ca +2 channels blockade, its extract was tested on K + (80 mM)-induced contractions which is known to cause smooth muscles contractions through opening of the voltage dependent L-type Ca +2 channels, thus allowing the influx of extracellular Ca +2 causing a contractile effect (Bolton, 1979) and substances inhibiting the K + (80 mM)-induced contraction are known as Ca +2 channels blockers, i.e., inhibitor of Ca +2 influx (Godfraind et al, 1986;Okumura et al, 1993;Shah et al, 2011). Crude extract of B. wallichiana, like verapamil (standard calcium channel blocker), relaxed the K + (80 mM)-induced contractions, indicating the Ca +2 channel blocking action.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological basis for the folkloric uses of Buxus wallichiana in gastrointestinal, respiratory and vascular disorders

Hussain

Raza

Janbaz

2015

Bangladesh J Pharmacol

View full text Add to dashboard Cite

In vitro study was carried out to explore the pharmacological basis of crude extract of Buxus wallichiana for its folkloric uses in gastrointestinal, respiratory and vascular disorders. In jejunum preparations, crude extract (0.03 ± 1.0 mg/mL) caused a transient spasmogenic effect followed by the spasmolytic effect at higher doses (3.0–10 mg/mL). In atropinized jejunum preparation, crude extract inhibited the spontaneous and K+ (80 mM)-induced contraction, suggesting that spasmolytic effect is mediated through the Ca+2-channel blockade. The Ca+2-channel blockade effect was confirmed when pretreatment of tissue with extract produced a dose-dependent shift in Ca+2 concentration-response curves to the right, similarly as verapamil. Furthermore, crude extract exhibited non-specific relaxant effect on carbachol- (1 µM) and K+ (80 mM)-induced tracheal contractions, suggesting the coexistence of anticholi-nergic and Ca+2-antagonistic properties. Moreover, it relaxed the K+ (80 mM)- and phenylephrine (1 µM)-induced contraction in rabbit aorta, suggesting the Ca+2-channel blockade. These findings may validate the folkloric uses of B. wallichiana in constipation, bronchitis, asthma and hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacological basis for the folkloric uses of Buxus wallichiana in gastrointestinal, respiratory and vascular disorders

Hussain

Raza

Janbaz

2015

Bangladesh J Pharmacol

View full text Add to dashboard Cite

show abstract

“…In isolated rat aortic tissues, L. culinaris extract was screened against high K + and phenylephrineinduced contractions. L. culinaris relaxed high K + and phenylephrine-induced contractions in aortic rings, indicating that it was acting through blockade of voltage-and receptor-operated Ca ++ channels (Okmura et al, 1993;Musha et al, 2005;Khan et al, 2013). As L.…”

Section: Discussionmentioning

confidence: 96%

Cardiovascular inhibitory properties of Lens culinaris

Khan¹,

Khan²,

Rehman³

et al. 2014

Bangladesh J Pharmacol

View full text Add to dashboard Cite

“…Aranidipine and its metabolites inhibited Ca2+ -induced contractions in the rabbit thoracic aorta depolarized with KC1 in a concentration-dependent manner (29). As shown in Table 1, (S) aranidipine was 148 times more potent than (R) aranidipine.…”

Section: Pharmacology Calcium Antagonistic Actionmentioning

confidence: 88%

Aranidipine (MPC‐1304), a New Dihydropyridine Calcium Antagonist: A Review of Its Antihypertensive Action

Ohashi

Ebihara

1996

Cardiovascular Drug Reviews

View full text Add to dashboard Cite

Key Words: Aranidipine-Antihypertensive agentxalcium channel antagonist.Calcium antagonists play an important role in the treatment of patients with cardiovascular diseases such as ischemic heart disease, heart failure, and hypertension. The dihydropyridine-type calcium antagonists are widely used to treat hypertension, because of their potent vasodilating activity and weak cardiodepressant action (9,38,11). Aranidipine (MPC-1304) is a novel dihydropyridine-type calcium antagonist, which is characterized by its active metabolites, once daily administration to facilitate patient compliance, and the prospect of good efficacy and safety. In experimental animal models aranidipine had more potent antihypertensive effects than did other dihydropyridines. Administration of aranidipine once daily had a highly potent antihypertensive effect and clinical utility in all of the clinical trials conducted in Japan. Aranidipine is now under registration. In this article, the pharmacological, toxicological, pharmacokinetic profiles, and clinical findings of aranidipine are reviewed. CHEMISTRY Aranidipine was first synthesized by Ohno et al. (24,25). The chemical structures of aranidipine [(+)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate] and its active metabolite, M-1 [2-hydroxypropyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate] , are shown in Fig. 1. Aranidipine has an asymmetric carbon at the C-4 position of the dihydropyridine ring. M-1 has two asymmetric carbons in its structure, and there exist four enantiomers: (S,S)-and (R,R)-M-1 (their mixture is M-l(a)), and (S,R)-and (R,S)-M-1 (their mixture is M-l(P)). The molecular weight of aranidipine (C19Hz,Nz0,) is 388.38, and its melting point is 149-150°C. Aranidipine is freely soluble in acetone and insoluble in water.

show abstract

Calcium entry blocking activities of MPC-1304 and of its enantiomers and metabolites

Cited by 15 publications

References 11 publications

Pharmacological basis for the folkloric uses of <i>Buxus wallichiana</i> in gastrointestinal, respiratory and vascular disorders

Pharmacological basis for the folkloric uses of <i>Buxus wallichiana</i> in gastrointestinal, respiratory and vascular disorders

Cardiovascular inhibitory properties of <i>Lens culinaris</i>

Aranidipine (MPC‐1304), a New Dihydropyridine Calcium Antagonist: A Review of Its Antihypertensive Action

Contact Info

Product

Resources

About