Bifemelane: Difference between revisions

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

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| tradename = Alnert, Celeport

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| synonyms = MCl-2016

'''Bifemelane''' ([[International Nonproprietary Name|INN]]) ('''Alnert''', '''Celeport'''), or '''bifemelane hydrochloride''' ([[Japanese Accepted Name|JAN]]), also known as '''4-(''O''-benzylphenoxy)-''N''-methylbutylamine''', is an [[antidepressant]] and [[cerebral activator]] that was widely used in the treatment of [[cerebral infarction]] patients with [[depression (mood)|depressive]] symptoms in Japan, and in the treatment of [[senile dementia]] as well.<ref name="pmid8846747">{{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 }}</ref><ref name="isbn0-412-46630-9">{{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}}</ref> It also appears to be useful in the treatment of [[glaucoma]].<ref>{{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 }}</ref> It has been discontinued in Japan since 1998, when it was removed from the market reportedly for lack of effectiveness.<ref>{{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 }}</ref>

Bifemelane acts as a [[monoamine oxidase inhibitor]] of both [[isoenzyme]]s, with competitive (reversible) inhibition of [[Monoamine oxidase A|MAO-A]] (K_i = 4.20&nbsp;''μ''M) (making it a [[reversible inhibitor of monoamine oxidase A]] (RIMA)) and non-competitive (irreversible) inhibition of [[Monoamine oxidase B|MAO-B]] (K_i = 46.0&nbsp;''μ''M),<ref name="NaoiNomura1988">{{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 }}</ref><ref name="Kovel'manTochilkin1991">{{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}}</ref><ref name="Choe2011">{{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}}</ref> and also acts (weakly) as a [[norepinephrine reuptake inhibitor]].<ref name="Dostert1994">{{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. }}</ref> The drug has [[nootropic]], [[neuroprotective]], and [[antidepressant]]-like effects in [[animal model]]s, and appears to enhance the [[cholinergic]] system in the [[brain]].<ref>{{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 }}</ref><ref>{{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 }}</ref><ref name="pmid8361950">{{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 }}</ref>

{{reflist|30em}}

{{Antidepressants}}

{{Adrenergics}}

{{Dopaminergics}}

{{Serotonergics}}

[[Category:Amines]]

[[Category:Antidepressants]]

[[Category:Monoamine oxidase inhibitors]]

[[Category:Norepinephrine reuptake inhibitors]]

[[Category:Reversible inhibitors of MAO-A]]

[[Category:Benzhydryl compounds]]

[[Category:Cerebral activators]]