Mibefradil

Mibefradil
Clinical data
Trade names	Posicor
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a607007
Routes of; administration	By mouth (tablets)
ATC code	C08CX01 (WHO) ;
Legal status
Legal status	Withdrawn from market;
Pharmacokinetic data
Bioavailability	70%
Protein binding	>99%
Metabolism	Liver (CYP3A4)
Elimination half-life	17–25 hours
Identifiers
	IUPAC name (1S,2S)-2-(2-((3-(1H-benzo[d]imidazol-2-yl)propyl) (methyl)amino)ethyl)-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl 2-methoxyacetate;
CAS Number	116644-53-2 ;
PubChem CID	60662;
IUPHAR/BPS	2522;
DrugBank	DB01388 ;
ChemSpider	54673 ;
UNII	27B90X776A;
KEGG	D08217 ;
ChEMBL	ChEMBL45816 ;
PDB ligand	MWV (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID1023318 ;
Chemical and physical data
Formula	C29H38FN3O3
Molar mass	495.639 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	128 °C (262 °F) (dihydrochloride salt)
	SMILES CC(C)[C@H]1C2=C(CC[C@@]1(CCN(C)CCCC3=NC4=CC=CC=C4N3)OC(=O)COC)C=C(C=C2)F;
	InChI InChI=1S/C29H38FN3O3/c1-20(2)28-23-12-11-22(30)18-21(23)13-14-29(28,36-27(34)19-35-4)15-17-33(3)16-7-10-26-31-24-8-5-6-9-25(24)32-26/h5-6,8-9,11-12,18,20,28H,7,10,13-17,19H2,1-4H3,(H,31,32)/t28-,29-/m0/s1 ; Key:HBNPJJILLOYFJU-VMPREFPWSA-N ;
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Mibefradil (trade name Posicor) was a pharmaceutical drug used for the treatment of hypertension and chronic angina pectoris. It is a nonselective calcium channel blocker. It was voluntary pulled from the market ten months after FDA approval, citing potential serious health hazards shown in post release studies.[1]

The mechanism of action of mibefradil is characterized by the selective blockade of transient, low-voltage-activated (T-type) calcium channels over long-lasting, high-voltage-activated (L-type) calcium channels,[1] which is probably responsible for many of its unique properties.

On June 8, 1998, Roche announced the voluntary withdrawal of the drug from the market, one year after approval by the FDA, due to the potential for drug interactions, some of them deadly, which may occur when it is taken together with some other medications.[2]

Synthesis

Mibefradil synthesis: YU 22988 ZW 20087

References

Bezprozvanny I, Tsien RW (September 1995). "Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967)". Mol. Pharmacol. 48 (3): 540–9. PMID 7565636.
Stolberg, Sheryl Gay (1998-06-09). "Heart Drug Withdrawn as Evidence Shows It Could Be Lethal". The New York Times. Retrieved 2019-01-12.

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[pmid7565636-1] Bezprozvanny I, Tsien RW (September 1995). "Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967)". Mol. Pharmacol. 48 (3): 540–9. PMID 7565636.

[Stolberg_1998-2] Stolberg, Sheryl Gay (1998-06-09). "Heart Drug Withdrawn as Evidence Shows It Could Be Lethal". The New York Times. Retrieved 2019-01-12.