bifemelane

{{Short description|Antidepressant and cerebral activator drug}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 459721492

| IUPAC_name = N-methyl-4-[2-(phenylmethyl)phenoxy]butan-1-amine

| image = Bifemelane.svg

| width = 235

| tradename = Alnert, Celeport

| Drugs.com = {{drugs.com|international|bifemelane}}

| routes_of_administration =

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

| CAS_number = 90293-01-9

| ATC_prefix = N06

| ATC_suffix = AX08

| PubChem = 2377

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

| ChEMBL = 1192517

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = Z4501GN13G

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 2286

| smiles = O(c1ccccc1Cc2ccccc2)CCCCNC

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C18H23NO/c1-19-13-7-8-14-20-18-12-6-5-11-17(18)15-16-9-3-2-4-10-16/h2-6,9-12,19H,7-8,13-15H2,1H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = QSQQPMHPCBLLGX-UHFFFAOYSA-N

| synonyms = MCl-2016, 4-(O-benzylphenoxy)-N-methylbutylamine

| C = 18

| H = 23

| N = 1

| O = 1

}}

Bifemelane (INN), sold under the brand names Alnert and Celeport, is an antidepressant and cerebral activator that was widely used in the treatment of cerebral infarction patients with depressive symptoms in Japan, and in the treatment of dementia as well.{{cite journal | vauthors = Koide S, Onishi H, Hashimoto H, Kai T, Katayama M, Yamagami S | title = Effects of bifemelane hydrochloride on plasma neuropeptide Y, 3-methoxy-4-hydroxyphenylethylene glycol and 5-hydroxy-indole acetic acid concentrations in patients with cerebral infarction | journal = Drugs Under Experimental and Clinical Research | volume = 21 | issue = 5 | pages = 175–80 | year = 1995 | pmid = 8846747 }}{{cite book | vauthors = Triggle DJ | title = Dictionary of Pharmacological Agents | publisher = Chapman & Hall/CRC | location = Boca Raton | year = 1996 | page = 265 | isbn = 978-0-412-46630-4 | url = https://books.google.com/books?id=DeX7jgInYFMC&q=bifemelane%20Alnert%20Celeport&pg=RA1-PA265}} It also appears to be useful in the treatment of glaucoma.{{cite journal | vauthors = Shigemitsu T, Majima Y | title = Use of bifemelane hydrochloride in improving and maintaining the visual field of patients with glaucoma | journal = Clinical Therapeutics | volume = 18 | issue = 1 | pages = 106–13 | year = 1996 | pmid = 8851457 | doi = 10.1016/S0149-2918(96)80183-4 }} It has been discontinued in Japan since 1998, when it was removed from the market reportedly for lack of effectiveness.{{cite journal | vauthors = Hayashi K, Hashimoto K, Yanagi M, Umeda T, Hama R | title = Drug approval in Japan questioned | journal = Lancet | volume = 352 | issue = 9126 | pages = 491 | date = August 1998 | pmid = 9708787 | doi = 10.1016/S0140-6736(05)79232-1 }}

Bifemelane acts as a monoamine oxidase inhibitor (MAOI) of both isoenzymes, with competitive reversible inhibition of MAO-A (K_i = 4.20 μM), making it a reversible inhibitor of monoamine oxidase A (RIMA) and non-competitive irreversible inhibition of MAO-B (K_i = 46.0 μM),{{cite journal | vauthors = Naoi M, Nomura Y, Ishiki R, Suzuki H, Nagatsu T | title = 4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy)-N-methylalkylamines as new inhibitors of type A and B monoamine oxidase | journal = Journal of Neurochemistry | volume = 50 | issue = 1 | pages = 243–7 | date = January 1988 | pmid = 3335842 | doi = 10.1111/j.1471-4159.1988.tb13256.x | s2cid = 35543291 }}{{cite journal| vauthors = Kovel'man IR, Tochilkin AI, Gorkin VZ |title=Structure and action of reversible monoamine oxidase inhibitors (review)|journal=Pharmaceutical Chemistry Journal|volume=25|issue=8|year=1991|pages=505–520|issn=0091-150X|doi=10.1007/BF00777412|s2cid=42477788}}{{cite book| vauthors = Choe JY |title=Drug Actions and Interactions |url= https://books.google.com/books?id=BZeTPw_GgbgC|date=4 March 2011|publisher=McGraw Hill Professional|isbn=978-0-07-176945-7|page=307}} and also acts (weakly) as a norepinephrine reuptake inhibitor (NEI).{{cite book | vauthors = Dostert P | chapter = Can our knowledge of monoamine oxidase (MAO) help in the design of better MAO inhibitors? | title = Amine Oxidases: Function and Dysfunction | journal = Journal of Neural Transmission. Supplementum | issue = Supplementum | volume = 41 | pages = 269–279 | year = 1994 | pmid = 7931236 | doi = 10.1007/978-3-7091-9324-2_35 | isbn = 978-3-211-82521-1 | quote = For example, bifemelane [4-(O-benzylphenoxy)-N-methylbutylamine) is one of the few molecules in which both activities, reversible inhibition of MAO-A (Naoi et al., 1988) and inhibition of noradrenaline uptake (Egawa et al., 1983), although weak (IC50 = 10-6-10-7 M), coexist. }} The drug has nootropic, neuroprotective, and antidepressant-like effects in animal models, and appears to enhance the cholinergic system in the brain.{{cite journal | vauthors = Kondo Y, Ogawa N, Asanuma M, Matsuura K, Nishibayashi K, Iwata E | title = Preventive effects of bifemelane hydrochloride on decreased levels of muscarinic acetylcholine receptor and its mRNA in a rat model of chronic cerebral hypoperfusion | journal = Neuroscience Research | volume = 24 | issue = 4 | pages = 409–14 | date = March 1996 | pmid = 8861111 | doi = 10.1016/0168-0102(95)01017-3 | s2cid = 34313096 }}{{cite journal | vauthors = Egashira T, Takayama F, Yamanaka Y | title = Effects of bifemelane on muscarinic receptors and choline acetyltransferase in the brains of aged rats following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries | journal = Japanese Journal of Pharmacology | volume = 72 | issue = 1 | pages = 57–65 | date = September 1996 | pmid = 8902600 | doi = 10.1254/jjp.72.57 | doi-access = free }}{{cite journal | vauthors = Moryl E, Danysz W, Quack G | title = Potential antidepressive properties of amantadine, memantine and bifemelane | journal = Pharmacology & Toxicology | volume = 72 | issue = 6 | pages = 394–7 | date = June 1993 | pmid = 8361950 | doi = 10.1111/j.1600-0773.1993.tb01351.x }}