Mibefradil

{{Short description|Withdrawn antihypertensive drug of the calcium channel blocker class}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 407797796

| 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

| image = Mibefradil.svg

| width = 275

| tradename = Posicor

| Drugs.com = {{drugs.com|CONS|mibefradil}}

| MedlinePlus = a607007

| pregnancy_category =

| legal_status = Withdrawn from market

| routes_of_administration = By mouth (tablets)

| bioavailability = 70%

| protein_bound = >99%

| metabolism = Liver (CYP3A4)

| elimination_half-life = 17–25 hours

| excretion =

| IUPHAR_ligand = 2522

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 116644-53-2

| ATC_prefix = C08

| ATC_suffix = CX01

| PubChem = 60662

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB01388

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = 27B90X776A

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D08217

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 45816

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 54673

| PDB_ligand = MWV

| C=29 | H=38 | F=1 | N=3 | O=3

| 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

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = HBNPJJILLOYFJU-VMPREFPWSA-N

| melting_point = 128

| melting_notes = (dihydrochloride salt)

}}

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.{{cite journal |vauthors=Bezprozvanny I, Tsien RW |title=Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967) |journal=Mol. Pharmacol. |volume=48 |issue=3 |pages=540–9 |date=September 1995 |pmid=7565636 |url=http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7565636}}

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, which is probably responsible for many of its unique properties.{{fact|date=April 2022}}

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.{{cite web | last=Stolberg | first=Sheryl Gay | title=Heart Drug Withdrawn as Evidence Shows It Could Be Lethal | website=The New York Times | date=1998-06-09 | url=https://www.nytimes.com/1998/06/09/us/heart-drug-withdrawn-as-evidence-shows-it-could-be-lethal.html | access-date=2019-01-12}}