Bifemelane hydrochloride

Bifemelane hydrochloride is a potent, selective and competitive inhibitor of monoamine oxidase A (MAO-A), with a Ki of 4.20 μM, and it also inhibits MAO-B noncompetitively with a Ki of 46.0 μM. Bifemelane hydrochloride has a potent antidepressant activity and can be used for the research of cognitive and emotional disturbances related to cerebrovascular disease[1][2].

Signaling Pathways >> Neuronal Signaling >> Monoamine Oxidase

Research Areas >> Neurological Disease

MAO-A:4.2 μM (Ki)

MAO-B:46 μM (Ki)

Bifemelane inhibits MAO-A in a dose-dependent manner, with Kis of 4.2±0.2 and 14.1±0.7 μM in human brain synaptosomes and human liver mitochondria respectively[1]. Bifemelane inhibits MAO-B activities in a dose-dependent manner, with Kis of 46.0±3.6 and 65.2±7.0 μM in human brain synaptosomes and human liver mitochondria respectively[1].

Bifemelane (20-80 mg/kg; i.p.) dose-dependently decreases exploratory activity in the open field test[3]. Bifemelane (20-80 mg/kg; i.p.) decreases immobility time in the forced swim test, although is not clearly dosedependent and has already reached ceiling at 20 mg/kg[3]. Animal Model: Wistar male rats (230-270 g) are induced hypothermia by Reserpine[3] Dosage: 20, 40, 80 mg/kg Administration: A single i.p. Result: Attenuated the Reserpine-induced hypothermia by a maximum of 10 ℃.

[1]. Naoi M, et, al. 4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy)-N-methylalkylamines as new inhibitors of type A and B monoamine oxidase. J Neurochem. 1988 Jan; 50(1): 243-7.

[2]. Fasipe OJ, et, al. The emergence of new antidepressants for clinical use: Agomelatine paradox versus other novel agents. IBRO Rep. 2019 Jan 9; 6:95-110.

[3]. Moryl E, et, al. Potential antidepressive properties of amantadine, memantine and bifemelane. Pharmacol Toxicol. 1993 Jun; 72(6): 394-7.

MOLECULAR FORMULA :

C18-H23-N-O.Cl-H

MOLECULAR WEIGHT :

305.88

WISWESSER LINE NOTATION :

1M4OR B1R &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1080 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - muscle weakness

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1278,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

130 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - muscle weakness

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1278,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

513 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 31,587,1986

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

40400 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 31,587,1986

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :

CCCCAK Collection of Czechoslovak Chemical Communications. (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1929- Volume(issue)/page/year: 53,1307,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

105 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,1181,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

313 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 31,587,1986

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

35300 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 31,587,1986

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

151 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - food intake (animal) Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

SHNSAS Shinryo to Shinyaku. Medical Consultation and New Remedies. (Iji Shuppan Sha, 1-2-8 Shinkawa, Chuo-Ku, Tokyo 104, Japan) V.1- 1964- Volume(issue)/page/year: 23,43,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

11375 mg/kg/13W-C

TOXIC EFFECTS :

Liver - fatty liver degeneration Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 31,587,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9100 mg/kg/52W-C

TOXIC EFFECTS :

Liver - fatty liver degeneration Kidney, Ureter, Bladder - other changes in urine composition Blood - changes in erythrocyte (RBC) count

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 31,601,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

24 gm/kg/52W-I

TOXIC EFFECTS :

Liver - changes in liver weight Blood - changes in leukocyte (WBC) count Related to Chronic Data - death

REFERENCE :

SHNSAS Shinryo to Shinyaku. Medical Consultation and New Remedies. (Iji Shuppan Sha, 1-2-8 Shinkawa, Chuo-Ku, Tokyo 104, Japan) V.1- 1964- Volume(issue)/page/year: 23,57,1986