Mibefradil

The LVA ai subunits are blocked by moderate to low (10 pM) concentrations of nickel and bind the channel blocker mibefradil and kurotoxin. Both compounds are not specific LVA channel blockers because they block also Cavl. x and Cav2.x channels at about tenfold higher concentration. Interestingly, the endogenous cannabinoid anandamide binds to LVA channels and stabilises the inactivated state. This effect decreases T-type calcium current and neuronal firing activities. 

C2H4 74-85-1) see Maprotiline Mibefradil hydrochloride Thioctic acid ethylene carbonate... 

C13H15FO 104204-91-3) see Mibefradil hydrochloride 9-fluoro-2,3-dihydro-.10-(4-methyl-l-piperazinyl)-7-oxo-7//-pyrido[l,2,3-dc]-l,4-benzothiazinc-6-carboxylic acid I Oxide... 

C4H7CIO 79-30-1) see Atorvastatin calcium Flutamide Ibopamine Mibefradil hydrochloride Ritonavir isochroman... 

QHgN2 95-54-5) see Benperidol Droperidol Mibefradil hydrochloride Pyrazinamide Tiabendazole Tibezonium iodide... 

C7H7CIO2S 98-59-9) see Benproperine Brinzolamide Carzenide Cefoxitin Diazepam Flurotyl Fosinopril Gusperimus trihydrochloride Idarubicin Idoxuridine Indeloxacine Levocabastine Mazindol Medazepam Mibefradil hydrochloride Nemonapride Pioglitazone Prenalterol Ropinirole Tinidazole Tolterodine p-toluenesulfonamide... 

Mibefradil (POSICOR) Asymmetric hydrogenation of a-acylaminoacrylic acids with Stinson (1996)... 

Crameri et al. (1997) have reported an asymmetric hydrogenation constituting an important step in the production of a new calcium antagonist, Mibefradil (POSICOR) (of Hoffmann-LaRoche). Pilot-scale synthesis of (S)-2-(4-flurophenyl)-3-methylbutanoic acid by the asymmetric hydrogenation of 2-(4-fluorophenyl)-3-methyl but-2-enoic acid with a [Ru (/ )-MeOBIPHEP)(OAc)2]-catalyst has been described. The hydrogenation was performed in a continuous mode in a cascade stirred-tank reactor system at a pressure of 270 bar. A large reduction in total reactor volume compared to the batch mode was realized. 

The two most frequently studied compounds with T-type calcium channel antagonist properties are ethosuximide 1 and mibefradil 3. However, the modest potency of ethosuximide ( 200 pM) [48] and the poor selectivity of mibefradil [49] make these compounds suboptimal tools for the investigation of these channels. Guided by a pharmacophore model [50], several analogs of 3 were prepared. Compound 4 represents the most potent compound identified (IC50 8 nM, patch-clamp assay) with good selectivity over the L-type calcium channel [51], Compound 4 showed a modest brain-to-plasma ratio (0.25) after oral dosing to rats at 50 mg/kg. However, no in vivo efficacy assay results have been reported with this compound. 

Berfhold, H. (1998) Riickruf von Cerate (Mibefradil) angeordnet Arzneimittelkommission der Deutschen Arzteschaftf. 

ADR Costartcode Flunarizine diHCI Fluoxetine HCI Mibefradil Nicardipine HCI Pinaverium Bromide Prenylamine Lactate Salt Raloxifene... 

Mibefradil Posicor Roche Laboratories Blood pressure, cardiovascular 6/20/1997 6/8/1998 1 year Drug interaction. Not available lowered heart rate in women ... 

However, the reverse is not necessarily true all compounds that block the hERG channels do not prolong action potentials. Part of the reason lies in the fact that many compounds have a mixed effect on ion channels, particularly due to the blocking effect on both hERG and the L-type calcium channel [21], which is responsible for phase 2 of the cardiac action potential (Figure 16.1). Examples for such dual-blockers include bepridil, verapamil and mibefradil [22], all blocking hERG and L-type calcium channels at the therapeutic concentrations. However, only verapamil has nearly no cardiac liabilities. 

The apparent liability of bepridil and mibefradil seems to result from their additional blocking effect on another important ion channel, KvLQTl/minK [23], which is responsible for phase 3 of the action potential (Figure 16.1). Indeed, the IKs blockers prolong the cardiac APD and QT interval and suppress electrically induced... 

---