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Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Mibefradil is a calcium channel blocker. No studies of this drug in human pregnancy of this are published. Heart defects were increased in frequency in rodents exposed to three times the usual human dose of mibefradil during organogenesis (Manufacturer package insert). It is an FDA pregnancy category C drug by the old system.
Inhibitors of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
NNC55-0396 (Ki = 2.8 nM) and Ro40-5966 (Ki = 4.5 nM), two novel calcium channel blocker of mibefradil analogs, have a three- to fourfold greater inhibitory activity toward recombinant CYP2D6 than mibefradil (Ki = 12.7 nM) (Figure 4.12) (Bui et al. 2008). Temsirolimus and its principal metabolite, sirolimus, inhibit the CYP2D6 with Ki of 1.5 and 5 μM, respectively (Boni et al. 2009b). Temsirolimus does not alter the pharmacokinetics of desipramine in vivo (Boni et al. 2009b). Temsirolimus is a novel inhibitor of mammalian target of rapamycin, which has been approved for treatment of renal cell carcinoma. Mirodenafil, a novel PDE5 inhibitor, inhibits CYP2D6 with an IC50 of 77 μM (Lee et al. 2008).
Inhibition of B16F10 Cancer Cell Growth by Exposure to the Square Wave with 7.83+/-0.3Hz Involves L- and T-Type Calcium Channels
Published in Electromagnetic Biology and Medicine, 2021
Min-Haw Wang, Ming-Wei Jian, Yuan-Hsuan Tai, Ling-Sheng Jang, Chun-Hong Chen
The findings of this study demonstrated that exposure to the square wave can alter the permeability of VGCCs and increase the influx of Ca2+ to suppress the proliferation of B16F10 cells. Inhibition of L- and T-type Ca2+ channels confirmed a greater influx of Ca2+ influx through the T-type Ca2+ channels than through the L-type Ca2+ channels, whereas the blockade of L- and T-type Ca2+ channels only suppressed a small part of the Ca2+ uptake. Mibefradil, an inhibitor of L- and T-type Ca2+ channels, inhibited Ca2+ influx by 24% (0.5 h exposure) and 13% (1 h exposure) when compared to control cells. Most of the Ca2+ could therefore be released from the ER by the CICR mechanism. These observations show that the square wave with 7.83±0.3 Hz could represent a potential anti-cancer therapy.
Synthesis and biological evaluation of pyrrolidine-based T-type calcium channel inhibitors for the treatment of neuropathic pain
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Hak Kyun Yang, Woo Seung Son, Keon Seung Lim, Gun Hee Kim, Eun Jeong Lim, Changdev G. Gadhe, Jae Yeol Lee, Kyu-Sung Jeong, Sang Min Lim, Ae Nim Pae
Based on these observations, it was believed that T-type calcium channel inhibitors would provide effective treatment options for neuropathic pain13, leading to development of a variety of T-type calcium channel blockers, such as Mibefradil25, ethosuximide26, and (3β,5α,17β)-17-hydroxyestrane-3-carbonitrile (ECN)27. In fact, treatment of Mibefradil or ethosuximide in the rat CCI model relieved behavioural symptoms of neuropathic pain28. It was shown that ECN also alleviated mechanical and thermal hypersensitivity in rats with neuropathic pain29 and in diabetic ob/ob mice30. Although these early T-type channel inhibitors showed great promise for the treatment of neuropathic pain, however, they suffered relatively low selectivity against other ion channels, especially voltage-gated sodium channels in neurons raising adverse side effect issues25,31,32. Moreover, Mibefradil was withdrawn just 1 year after the FDA approval due to drug–drug interactions33.
Evaluation of index of cardio-electrophysiological balance in patients with coronary slow flow
Published in Acta Cardiologica, 2022
Beltrame et al. [12] performed a series of procedures such as coronary sinus cannulation and rapid atrial stimulation, cold stimulation, and acetylcholine infusion to determine endothelial dysfunction during CA and they found vasomotor tonus increased in CSF patients at rest. Mibefradil, a calcium channel blocker, reduces the anginal symptoms of the patients with the average TFC in patients with CSF, and this result has been interpreted as a result of the positive effects of mibefradil against endothelial dysfunction [13]. In the study conducted by Sezgin et al., flow-mediated enlargement of the brachial artery, which is an indicator of endothelial dysfunction, was found to be significantly lower in CSF patients [14].