Disease relevance of Bifemelane

• However, administration of the neuroprotective drug bifemelane (10 to 20 mg/kg, i.p.) resulted in prolongation of the potentiation of AP1 binding in the CA1 subfield up to 6 hr after ischemia, without significantly affecting that in other central structures [1].
• It has been shown that dysfunction of the cholinergic neuronal system plays an important role in memory loss and that bifemelane induces recovery of reduced cerebral cholinergic neuronal activity associated with brain ischemia or aging [2].
• The effects of bifemelane on parkinsonism were shown in MPTP-treated common marmosets [3].
• The present findings suggest a beneficial effect of bifemelane on neuronal ischemia-reperfusion injury, which may be common after cerebral ischemia [4].
• We examined the protective effects of bifemelane HCl and the relation between its effectiveness and free radical formation in hydrogen peroxide (H2O2)-induced cytotoxicity using cultured rat neuroblastoma cell line (B50) [5].

Psychiatry related information on Bifemelane

• In accordance with these previous findings, our results suggest that bifemelane is useful in the treatment of memory loss and cognitive dysfunction in patients with dementia and cerebrovascular disease [2].
• When administered alone, neither bifemelane nor indeloxazine had an effect on the task performance of normal rats [2].
• The administration of bifemelane increased locomotor activity in MPTP-treated marmosets but not in normal control marmosets [3].
• Effects of bifemelane on discrimination learning of serotonergic-dysfunction rats [6].
• We suggested that amantadine and bifemelane could be particularly useful therapeutically when depressive symptoms are present in patients suffering from Parkinson's disease and dementia [7].

High impact information on Bifemelane

• 4-(O-Benzylphenoxy)-N-methylbutylamine (Bifemelane, BP-N-methylbutylamine), a new psychotropic drug, was found to inhibit monoamine oxidase (MAO) in human brain synaptosomes [8].
• Prolongation by bifemelane of potentiation of AP1 DNA binding in hippocampal CA1 subfield of gerbils with transient forebrain ischemia [1].
• Limited proteolysis revealed that bifemelane induced expression of the AP1 consisting of constructive proteins different from those expressed in control animals in the CA1 subfield [1].
• Bifemelane has an anti-amnesic effect, produces the translocation of protein kinase C in the hippocampal CA3 region but not in CA1 and enhances long-term potentiation in the mossy fibre-CA3 system but not in the Schaffer collateral-CA1 system [9].
• Specific binding sites for bifemelane in the hippocampus of the guinea pig, relevant to its pharmacological actions [9].

Chemical compound and disease context of Bifemelane

• Effects of bifemelane on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset [3].
• To examine the therapeutic effect of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane) on neuronal ischemia-reperfusion injury, we evaluated the neurological score in gerbils subjected to unilateral common carotid occlusion [4].
• In view of the findings that bifemelane markedly inhibits the decrease in acetylcholine (ACh) associated with cerebral ischemia, and that it improves amnesia induced by scopalamine, it may be inferred that bifemelane acts on the pre- and post-synaptic ACh neuronal systems [10].

Biological context of Bifemelane

• On the other hand, naloxone, an opioid antagonist, inhibited and bifemelane, which improves metabolism in brain and has an anti-amnesic action, augmented long-term potentiation in mossy fibre-CA3 system but did not influence those in commissural/associational fibre- and fimbrial fibre-CA3 systems [11].
• It is concluded that bifemelane can be used to improve visual acuity in many patients with central retinal artery obstruction [12].
• The magnitude of tetanus-induced LTP at the mossy fiber synapse was augmented by perfusion of slices with several cognitive enhancers, such as bifemelane (1 microM) [13].
• On the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to brain membranes, the estimated IC50 values were 88 microM for bifemelane, 102 microM for indeloxazine, and 115 microM for vinpocetine [14].
• Bifemelane has been demonstrated to inhibit acetylcholine release strongly during cerebral ischaemia but not interfere with normal cholinergic synaptic transmission [15].

Anatomical context of Bifemelane

• Bifemelane in the treatment of central retinal artery or vein obstruction [12].
• The use of Xenopus oocytes to evaluate drugs affecting brain Ca2+ channels: effects of bifemelane and several nootropic agents [16].
• Bifemelane (1 microM) induced the translocation of protein kinase C activity from cytosol to membrane in the P3 fraction (which contains large and irregular-shaped synaptosomes probably derived from mossy fiber terminals), but not in the P2 fraction [17].
• After treatment with bifemelane, improvements in visual acuity were seen in 12 of 17 eyes with central retinal artery obstruction, in three of four eyes with central retinal vein obstruction, and in five of nine eyes with branch retinal vein obstruction [12].
• Inhibitory effect of bifemelane on superoxide generation by activated neutrophils measured using a simple chemiluminescence method [18].

Associations of Bifemelane with other chemical compounds

• These findings suggest that bifemelane directly acts on mossy fiber terminals to potentiate depolarization-induced glutamate release, which may be at least partly mediated by the translocation (activation) of protein kinase C [17].
• Piracetam (10(-6) to 10(-4) M) and bifemelane (10(-8) to 10(-6) M) significantly augmented the LTP in the CA3 region [19].
• The effects of bifemelane [4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride] on the deposition of calcium and magnesium in central nervous system (CNS) tissues, heart, liver, kidney, muscle, abdominal aorta and bones were studied in rats maintained on standard and low-calcium diets [20].
• The effect of bifemelane hydrochloride (bifemelane) was examined on human origin astrocyte clonal cells (Kings-1) [21].

Gene context of Bifemelane

• In aged rats chronically administered bifemelane, the ChAT activity recovered to the level in the young rats in the cerebral cortex and hippocampus, and the M1-R level recovered completely in the cerebral cortex, hippocampus and striatum [22].
• Repeated administration of bifemelane hydrochloride (4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride) for 14 days increased the levels of beta-actin mRNA in the frontal cortex and the striatum of both young-adult and aged rats, although the effect of bifemelane treatment was smaller and not significant in the aged group [23].
• In an attempt to identify the changes induced in the synthesis of cytoskeletal protein by ischemia, we also evaluated the effects of post-ischemia administration of bifemelane on these cytoskeletal proteins. alpha-Tubulin and beta-actin mRNAs were decreased in the CA1 region 14 days after transient ischemia [24].
• Bifemelane suppressed the elevation of the lipid peroxide level, the cytochrome b5 content and the decrease in cytochrome P-450 content during the period of reperfusion [25].
• Immunohistochemistry using an antibody for microtubule-associated protein 2 clearly demonstrated preservation of staining especially in the caudate-putamen in the animals treated with bifemelane [4].

Analytical, diagnostic and therapeutic context of Bifemelane

• After the first PET scan, bifemelane was administered orally three times in a daily dose of 150 mg [26].
• Treatment with bifemelane after reperfusion significantly improved the neurological score and motor function [4].
• Pretreatment of B50 cells with 10 microM bifemelane for 2 days reduced lipid peroxide formation to approximately 54% of the control group [5].

References