New 1,4-dihydropyridine derivatives with potent and long-lasting hypotensive effect.

Calcium Channel Blocking Action of Franidipine Hydrochloride (CV-4093-2HCI) In Vitro and In Vivo

“…3 and 4). Moreover, the antihyper tensive effect of CV-4093.2HCI in SHR was more pronounced than that of nifedipine and nicardipine (6).…”

“…Okabe et al (7) have observed both phenomena (slow onset of the action and unwashable effect) in the inhibitory effect of CV-4093.2HC1 on the Ca inward current in single smooth muscle cells of the rabbit main pulmonary artery, which was examined by the single electrode voltage clamp method. Although the mechanisms related to these phenomena remain to be clarified, the hardly washable nature of CV 4093.2HC1 might partly contribute to the long antihypertensive action of this drug in SHR (6).…”

“…Nevertheless, we consider that at least two mechanisms may con tribute to these findings. First, the inhibitory effects of CV-4093.2HCI on the KCI-induced increase in perfusion pressure in the isolated, perfused kidney and mesenteric vascular beds might be due to the dilating effects on the resistance vessel-like arterioles, and this may be partly responsible for the more effective antihypertensive effect of CV-4093-21-10 in vivo in SHR as compared to those of nifedi pine and nicardipine (6). The findings of Cauvin and co-workers (15) that the distal portion of rabbit mesenteric artery exhibited a similar pharmacological response to that of the resistance artery may support this view.…”

“…Recently, Meguro et al (6) reported the synthesis of a new 1,4-dihydropyridine derivative, methyl 2-(4-diphenylmethyl-1 piperazinyl)ethyl (+)-1,4-dihydro-2,6-dime thyl-4-(m-nitrophenyl)-3,5-pyridine-dicar boxylate dihydrochloride (CV-4093.2HC1), with a potent and long-lasting antihyper tensive property in SHR. Okabe et al (7) have reported the inhibitory actions of CV 4093.2HC1 on the calcium current in single smooth muscle cells of rabbit main pulmonary artery, indicating that CV-4093.2HCI has highly selective and long-lasting inhibitory actions on the Ca++-induced current.…”

Effect of Compression on Interaction between 1,4-Dihydropyridine Compounds and Lactose Monohydrate

“…4) In the series of 1,4-dihydropyridines, the existences of polymorph and/or hydrate form have been reported in nicardipine hydrochloride, 5) nilvadipine 6) and manidipine dihydrochloride. 2) We have reported in the previous paper 7) that the dissolution behaviors of anhydrate and monohydrate forms of benidipine hydrochloride, which is one of the 1,4-dihydropyridines and has a similar structure of manidipine dihydrochloride. We also have reported 8) that during thermal treatment of physical mixtures of manidipine dihydrochloride or benidipine hydrochloride with lactose monohydrate, the interaction was observed between them but not with lactose anhydrate.…”