Bifemelane Explained

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 (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),^{[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

• Indeloxazine
• Teniloxazine

Notes and References

1. Koide S, Onishi H, Hashimoto H, Kai T, Katayama M, Yamagami S . 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 . 1995 . 8846747 .
2. Book: Triggle DJ . Dictionary of Pharmacological Agents . Chapman & Hall/CRC . Boca Raton . 1996 . 265 . 978-0-412-46630-4 .
3. Shigemitsu T, Majima Y . Use of bifemelane hydrochloride in improving and maintaining the visual field of patients with glaucoma . Clinical Therapeutics . 18 . 1 . 106–13 . 1996 . 8851457 . 10.1016/S0149-2918(96)80183-4 .
4. Hayashi K, Hashimoto K, Yanagi M, Umeda T, Hama R . Drug approval in Japan questioned . Lancet . 352 . 9126 . 491 . August 1998 . 9708787 . 10.1016/S0140-6736(05)79232-1 .
5. Naoi M, Nomura Y, Ishiki R, Suzuki H, Nagatsu T . 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 . January 1988 . 3335842 . 10.1111/j.1471-4159.1988.tb13256.x . 35543291 .
6. Kovel'man IR, Tochilkin AI, Gorkin VZ . Structure and action of reversible monoamine oxidase inhibitors (review). Pharmaceutical Chemistry Journal. 25. 8. 1991. 505–520. 0091-150X. 10.1007/BF00777412. 42477788.
7. Book: Choe JY . Drug Actions and Interactions . 4 March 2011. McGraw Hill Professional. 978-0-07-176945-7. 307.
8. Dostert P . Can our knowledge of monoamine oxidase (MAO) help in the design of better MAO inhibitors? . Journal of Neural Transmission. . Supplementum . 41 . 269–279 . 1994 . 7931236 . 10.1007/978-3-7091-9324-2_35 . 978-3-211-82521-1 . 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. ].
9. Kondo Y, Ogawa N, Asanuma M, Matsuura K, Nishibayashi K, Iwata E . 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 . March 1996 . 8861111 . 10.1016/0168-0102(95)01017-3 . 34313096 .
10. Egashira T, Takayama F, Yamanaka Y . 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 . September 1996 . 8902600 . 10.1254/jjp.72.57 . free .
11. Moryl E, Danysz W, Quack G . Potential antidepressive properties of amantadine, memantine and bifemelane . Pharmacology & Toxicology . 72 . 6 . 394–7 . June 1993 . 8361950 . 10.1111/j.1600-0773.1993.tb01351.x .