Bifemelane

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Bifemelane
Bifemelane.svg
Clinical data
Trade names Alnert, Celeport
Other namesMCl-2016
AHFS/Drugs.com International Drug Names
ATC code
Identifiers
  • N-methyl-4-[2-(phenylmethyl)phenoxy]butan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.220.566 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H23NO
Molar mass 269.388 g·mol−1
3D model (JSmol)
  • O(c1ccccc1Cc2ccccc2)CCCCNC
  • InChI=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 Yes check.svgY
  • Key:QSQQPMHPCBLLGX-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Bifemelane (INN) (Alnert, Celeport), or bifemelane hydrochloride (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 depressive symptoms in Japan, and in the treatment of senile dementia as well. [1] [2] It also appears to be useful in the treatment of glaucoma. [3] It has been discontinued in Japan since 1998, when it was removed from the market reportedly for lack of effectiveness. [4]

Bifemelane acts as a monoamine oxidase inhibitor of both isoenzymes, with competitive (reversible) inhibition of MAO-A (Ki = 4.20 μM) (making it a reversible inhibitor of monoamine oxidase A (RIMA)) and non-competitive (irreversible) inhibition of MAO-B (Ki = 46.0 μM), [5] [6] [7] and also acts (weakly) as a norepinephrine reuptake inhibitor. [8] The drug has nootropic, neuroprotective, and antidepressant-like effects in animal models, and appears to enhance the cholinergic system in the brain. [9] [10] [11]

See also

Related Research Articles

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<span class="mw-page-title-main">Tranylcypromine</span> Irreversible non-selective MAO inhibitor Antidepressant drug

Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

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<span class="mw-page-title-main">Imipramine</span> Antidepressant

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<span class="mw-page-title-main">Selegiline</span> Monoamine oxidase inhibitor

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<span class="mw-page-title-main">Nortriptyline</span> Antidepressant medication

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<span class="mw-page-title-main">Moclobemide</span> Antidepressant

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<span class="mw-page-title-main">Dosulepin</span> Antidepressant

Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects.

<span class="mw-page-title-main">Iproniazid</span> Antidepressant

Iproniazid is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class. It is a xenobiotic that was originally designed to treat tuberculosis, but was later most prominently used as an antidepressant drug. However, it was withdrawn from the market because of its hepatotoxicity. The medical use of iproniazid was discontinued in most of the world in the 1960s, but remained in use in France until its discontinuation in 2015.

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<span class="mw-page-title-main">Monoamine oxidase B</span> Protein-coding gene in the species Homo sapiens

Monoamine oxidase B, also known as MAO-B, is an enzyme that in humans is encoded by the MAOB gene.

<span class="mw-page-title-main">Nefopam</span> Analgesic medication

Nefopam, sold under the brand name Acupan among others, is a centrally acting, non-opioid painkilling medication, that is primarily used to treat moderate to severe pain.

<span class="mw-page-title-main">Indeloxazine</span> Antidepressant and cerebral activator

Indeloxazine (INN) is an antidepressant and cerebral activator that was marketed in Japan and South Korea by Yamanouchi Pharmaceutical Co., Ltd for the treatment of psychiatric symptoms associated with cerebrovascular diseases, namely depression resulting from stroke, emotional disturbance, and avolition. It was marketed from 1988 to 1998, when it was removed from the market reportedly for lack of effectiveness.

<span class="mw-page-title-main">Amiflamine</span> Chemical compound

Amiflamine (FLA-336) is a reversible inhibitor of monoamine oxidase A (MAO-A), thereby being a RIMA, and, to a lesser extent, semicarbazide-sensitive amine oxidase (SSAO), as well as a serotonin releasing agent (SRA). It is a derivative of the phenethylamine and amphetamine chemical classes. The (+)-enantiomer is the active stereoisomer.

<span class="mw-page-title-main">Caroxazone</span> Chemical compound

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<span class="mw-page-title-main">Almoxatone</span> Chemical compound

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<span class="mw-page-title-main">Bazinaprine</span> Chemical compound

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Sercloremine (CGP-4718A), usually as the hydrochloride salt, is a drug which was developed in the 1980s and was formerly under investigation as an antidepressant, but was never marketed. It acts as a selective, reversible inhibitor of monoamine oxidase A (RIMA) and serotonin reuptake inhibitor.

References

  1. Koide S, Onishi H, Hashimoto H, Kai T, Katayama M, Yamagami S (1995). "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". Drugs Under Experimental and Clinical Research. 21 (5): 175–80. PMID   8846747.
  2. Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. p. 265. ISBN   978-0-412-46630-4.
  3. Shigemitsu T, Majima Y (1996). "Use of bifemelane hydrochloride in improving and maintaining the visual field of patients with glaucoma". Clinical Therapeutics. 18 (1): 106–13. doi:10.1016/S0149-2918(96)80183-4. PMID   8851457.
  4. Hayashi, Keiji; Hashimoto, Kentaro; Yanagi, Motokazu; Umeda, Tadanori; Hama, Rokuro (August 1998). "Drug approval in Japan questioned". The Lancet. 352 (9126): 491. doi:10.1016/S0140-6736(05)79232-1.
  5. Naoi M, Nomura Y, Ishiki R, Suzuki H, Nagatsu T (January 1988). "4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy)-N-methylalkylamines as new inhibitors of type A and B monoamine oxidase". Journal of Neurochemistry. 50 (1): 243–7. doi:10.1111/j.1471-4159.1988.tb13256.x. PMID   3335842. S2CID   35543291.
  6. Kovel'man IR, Tochilkin AI, Gorkin VZ (1991). "Structure and action of reversible monoamine oxidase inhibitors (review)". Pharmaceutical Chemistry Journal. 25 (8): 505–520. doi:10.1007/BF00777412. ISSN   0091-150X. S2CID   42477788.
  7. Choe JY (4 March 2011). Drug Actions and Interactions. McGraw Hill Professional. p. 307. ISBN   978-0-07-176945-7.
  8. Dostert P (1994). "Can our knowledge of monoamine oxidase (MAO) help in the design of better MAO inhibitors?". Amine Oxidases: Function and Dysfunction. Vol. 41. pp. 269–279. doi:10.1007/978-3-7091-9324-2_35. ISBN   978-3-211-82521-1. PMID   7931236. 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.{{cite book}}: |journal= ignored (help)
  9. Kondo Y, Ogawa N, Asanuma M, Matsuura K, Nishibayashi K, Iwata E (March 1996). "Preventive effects of bifemelane hydrochloride on decreased levels of muscarinic acetylcholine receptor and its mRNA in a rat model of chronic cerebral hypoperfusion". Neuroscience Research. 24 (4): 409–14. doi:10.1016/0168-0102(95)01017-3. PMID   8861111. S2CID   34313096.
  10. Egashira T, Takayama F, Yamanaka Y (September 1996). "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". Japanese Journal of Pharmacology. 72 (1): 57–65. doi: 10.1254/jjp.72.57 . PMID   8902600.
  11. Moryl E, Danysz W, Quack G (June 1993). "Potential antidepressive properties of amantadine, memantine and bifemelane". Pharmacology & Toxicology. 72 (6): 394–7. doi:10.1111/j.1600-0773.1993.tb01351.x. PMID   8361950.