Effects Of Bifemelane Hydrochloride Research Articles

Bifemelane Hydrochloride Reduces Plasma β-Endorphin-Like Immunoreactivity Levels in Rats

The effect of bifemelane hydrochloride on plasma beta-endorphin-like immunoreactivity (beta-En-LI) levels in rats was studied. Bifemelane hydrochloride (25 mg/kg) was injected i.p., and the animals were decapitated at various times after the administration. The plasma beta-En-LI levels were measured by radioimmunoassay. The effect of bifemelane hydrochloride on beta-En-LI release from the anterior pituitary was also investigated by means of an in vitro experiment. The beta-En-LI content in the hypothalamus and pituitary gland did not change significantly after bifemelane hydrochloride injection. The plasma beta-En-LI levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. The beta-En-LI release in vitro from the anterior pituitary was inhibited with the addition of bifemelane hydrochloride. The findings suggest that bifemelane hydrochloride acts on the anterior pituitary to inhibit beta-En-LI release.

Effects of Bifemelane on the Calcium Level and ATP Release of the Human Origin Astrocyte Clonal Cell

The effect of bifemelane hydrochloride (bifemelane) was examined on human origin astrocyte clonal cells (Kings-1). Bifemelane (125 – 1000 µM) induced a dose-dependent increase in the intracellular calcium concentration ([Ca2+]i). In the highest concentration (1000 µM), the drug caused the second large increase in [Ca2+]i during the washing. The increase that occurred during the administration partially remained in the Ca2+-free medium and was blocked by 2-aminoethoxydiphenyl borate (2-APB), an IP3-receptor blocker, indicating that the source of Ca2+for the increase could be ascribed to the intracellular store. The increase in [Ca2+]i was not observed during washing with Ca2+-free medium, but was observed when the washing was performed with Ca2+-containing medium. Bifemelane caused a dose-dependent ATP release, but histamine and carbachol, which induced a large increase in [Ca2+]i, had no effects on the ATP release. The effects on the [Ca2+]i were blocked by pretreatment with pyridoxal phosphate-6-azophenyl-2’,4’ disulfonic acid, a P2-receptor antagonist. Although the mechanisms of ATP release induced by the drug have not been elucidated yet, the present results demonstrate that the increase in [Ca2+]i induced by bifemelane is not due to its direct effect on the cells, but is dependent upon the ATP released from the cells.

ミネラル偏食による動脈硬化症老齢ラットにおける中枢神経組織のカルシウムおよびアルミニウム代謝におよぼす4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride(bifemilane)の効果

ミネラル偏食による動脈硬化症老齢ラットにおける中枢神経組織のカルシウムおよびアルミニウム代謝におよぼす4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride(bifemilane)の効果

P3-232 - Effects of bifemelane hydrochloride on muscarinic receptors and choline acetyl transferase in brain of partial cerebrovascular insufficient aged rats

P3-232 - Effects of bifemelane hydrochloride on muscarinic receptors and choline acetyl transferase in brain of partial cerebrovascular insufficient aged rats

Reduction of HSP70 and HSC70 mRNA inductions by bifemelane hydrochloride after transient ischemia in gerbil brain

The effect of bifemelane hydrochloride (BFH) on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brain was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Following 3.5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The CA1 cells were almost lost by 7 days. Treatment with BFH twice before and after ischemia (total 60 mg/kg, i.p.) reduced the induction of HSP70 and HSC70 mRNAs both at 8 h and 1 day of the reperfusion, and about half of the CA1 cells survived at 7 days. Thus, the reduction of HSP70 and HSC70 mRNA inductions after ischemia may suggest that BFH reduced intra- and/or post-ischemic stress, and protected CA1 cells from ischemic damage.

Ischemia-induced changes in α-tubulin and β-actin mRNA in the gerbil brain and effects of bifemelane hydrochloride

Using in situ hybridization histochemistry, we examined changes in the cytoskeletal protein α-tubulin and β-actin mRNAs in the gerbil brain 14 days after transient ischemia. In an attempt to identify the changes induced in the synthesis of cytoskeletal protein by schemia, we also evaluated the effects of post-ischemia administration of bifemelane on these cytoskeletal proteins. α-Tubulin and α-actin mRNAs were decreased in the CA1 region 14 days after transient ischemia. These decreases coincided with the loss of CA1 pyramidal cells, suggesting that they may have been related to delayed neuronal death. The β-actin mRNA level in ischemic controls was significantly increased in the dentate gyrus, habenular nucleus, and medial and lateral thalamic nuclei, where some afferent nerves project into the hippocampal pyramidal cells. The increased β-actin mRNA suggests that there may be a compensatory enhancement of actin synthesis in the afferent neurons that restores loosened synaptic connections with the ischemic cells in the CA1-4 fields. Administration of bifemelane just after recirculation prevented most of the ischemia-induced mRNA reductions in the CA1 field. Bifemelane's effect may be related to inhibition of Ca 2+ influx and its radical scavenging activity. When bifemelane was administered to the ischemic group, α-tubulin mRNA levels significantly increased in the dentate gyrus and amygdaloid nucleus, and β-actin mRNAs showed a tendency to increase in the CA3 and CA4 fields, dentate gyrus, and medial and lateral thalamic nuclei. These findings suggest that bifemelane may enhance synthesis of cytoskeletal protein, especially in the ischemic brain, inducing axon outgrowth or synapse formation.

Effects of Bifemelane Hydrochloride, a Brain Function Improver, on Muscarinic Receptors in the CNS of Senescence-Accelerated Mouse.

Senescence-accelerated mouse (SAM-P/8) is known as a murine model of aging and memory dysfunction, compared with control mouse (SAM-R/1). In the hippocampus of 9-month-old SAM-P/8, the Bmax of [3H]QNB binding was decreased compared with that of SAM-R/1 at the same age. Single and repeated administrations of bifemelane to SAM-P/8 induced an increase in the Bmax of [3H]QNB binding in the hippocampus. From these results, bifemelane seems to exert pharmacological effects through possible activation of the cholinergic system in the hippocampus of SAM.

Clinical Effects of Bifemelane Hydrochloride on Hearing Losses in Meniere's Patients

The clinical effects of bifemelane hydrochloride on hearing loss were investigated in 16 patients with Meniere's disease (27 ears). The dosage was 150 mg of bifemelane hydrochloride (Alnert(R)) daily for 8 weeks to 10 months. The control group consisted of 26 patients with Meniere's disease (40 ears).1. Improvement of the hearing level was seen in 44.4 % of the ears of those treated with bifemelane hydrochloride at the 8 week point, when all subjects were examined. Great improvement was noted in 7.4% of the ears, moderate improvement in 3.7%6, and slight improvement in 33.3%. These results were significantly higher than those of the control group. Moreover, some level of improvement was seen in a total of 60.0% of 15 ears in 10 patients who received bifemelane for more than 5 month.2. The degree of improvement in hearing levels were greater in those with less than 60 dB hearing than in those with 60 dB and over hearing at the time of the 8 week examination.3. The efficacy of bifemalane hydrochloride was unrelated to the patient's age.

Effects of bifemelane hydrochloride on the experimental amnesia induced by the cholinergic dysfunction in rats

Effects of bifemelane hydrochloride on the experimental amnesia induced by the cholinergic dysfunction in rats

Effects of bifemelane hydrochloride on various cholinergic markers in brain of young and aged rats

Effects of bifemelane hydrochloride on various cholinergic markers in brain of young and aged rats

Effect of Bifemelane Hydrochloride on an Injury of the Liver Caused by Ischemia-Reperfusion in Rats

In the liver ischemia-reperfusion model, the lipid peroxide level increased during ischemic periods, while a greater increase was observed during reflow periods. The increase in the cytochrome b5 content was observed during ischemia and reflow periods. On the contrary, the cytochrome P-450 content remained unchanged during ischemic periods, but decreased during reflow periods. 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.

Effect of bifemelane hydrochloride on an injury of the liver caused by ischemia-reperfusion in rats.

In the liver ischemia-reperfusion model, the lipid peroxide level increased during ischemic periods, while a greater increase was observed during reflow periods. The increase in the cytochrome b5 content was observed during ischemia and reflow periods. On the contrary, the cytochrome P-450 content remained unchanged during ischemic periods, but decreased during reflow periods. 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.

Effects of Bifemelane Hydrochloride on Various Cholinergic Markers in Cortical and Subcortical Regions of Aged Rats

The effects of bifemelane hydrochloride (BF) upon various cholinergic markers, muscarinic receptors, acetylcholinesterase (AChE) and choline acetyl-transferase (CAT), in the aged rat brain were examined. Marked reduction of the density of muscarinic receptors (Bmax) as well as AChE and CAT activity concomitant with aging was observed. Administration of BF in daily doses of 10 mg/kg for 4 weeks to aged rats significantly decreased the apparent dissociation constant (K4) for QNB in muscarinic receptors in the forebrain, but did not affect the value of Bmax. CAT activity also increased significantly compared with that of control aged rats, but administration of BF did not alter AChE activity. These results indicate that long-term treatment with BF enhances the affinity of muscarinic receptors for QNB as well as CAT activity and that BF may have therapeutic application in the treatment of CNS cholinergic dysfunctions.

Effects of bifemelane hydrochloride on various cholinergic markers in cortical and subcortical regions of aged rats.

The effects of bifemelane hydrochloride (BF) upon various cholinergic markers, muscarinic receptors, acetylcholinesterase (AChE) and choline acetyltransferase (CAT), in the aged rat brain were examined. Marked reduction of the density of muscarinic receptors (Bmax) as well as AChE and CAT activity concomitant with aging was observed. Administration of BF in daily doses of 10 mg/kg for 4 weeks to aged rats significantly decreased the apparent dissociation constant (Kd) for QNB in muscarinic receptors in the forebrain, but did not affect the value of Bmax. CAT activity also increased significantly compared with that of control aged rats, but administration of BF did not alter AChE activity. These results indicate that long-term treatment with BF enhances the affinity of muscarinic receptors for QNB as well as CAT activity and that BF may have therapeutic application in the treatment of CNS cholinergic dysfunctions.

一過性アノキシア負荷後のＥＰの回復に対する塩酸ビフェメランの影響

一過性アノキシア負荷後のＥＰの回復に対する塩酸ビフェメランの影響

Effect of Bifemelane Hydrochloride on ABR and change of Cochlear in Anoxic guinea pigs

Effect of Bifemelane Hydrochloride on ABR and change of Cochlear in Anoxic guinea pigs

Effects of bifemelane hydrochloride on cortical neuronal activity in cats

The effects of bifemelane hydrochloride on neuronal activity in the visual cortex of the cat were studied by microiontophoretic application under methoxyflurane anesthesia. Of 195 neurons examined with both acetylcholine (ACh) and bifemelane, 67 cells (34%) were excited and 7 cells (4%) were inhibited by ACh. The effect of bifemelane was excitatory on 122 neurons (63%), inhibitory on 20 (10%) and unchanged on the rest. In 60 cells out of the above 122 neurons, bifemelane showed a similar discharge pattern to ACh with a slow onset and delayed termination. The bifemelane-induced excitation was, in 18 out of 22 cells, antagonized by atropine (30–40 nA). Also, a potentiation in bifemelane-induced discharges by physostigmine (30–50 nA) was observed in 14 of the 32 cells tested. The firing evoked by ACh (80–100nA) was potentiated during of after the application of bifemelane (30–40 nA) in 9 out of 29 neurons, which were not excited by bifemelane alone. These results suggest that neuronal discharges produced by bifemelane are induced at least in part, through a muscarinic ACh receptor, although other mechanisms may possibly be involved.

Effects of Bifemelane Hydrochloride (MCI-2016) on Acetylcholine Level Reduced by Scopolamine, Hypoxia and Ischemia in the Rats and Mongolian Gerbils

Effects of bifemelane hydrochloride (MCI-2016) on acetylcholine (ACh) level in the cerebral cortex and hippocampus of rats and Mongolian gerbils were examined. In normal rats, MCI-2016 (30 mg/kg, i.p.) slightly increased ACh content in the cerebral cortex. Scopolamine (1 mg/kg, i.p.) or hypoxia (95% N2 + 5% O2, 9 min) decreased ACh level and pretreatment of MCI-2016 attenuated the decrement of ACh level in the rats. ACh level in the brain of Mongolian gerbils was significantly decreased following ligation of bilateral carotid arteries. In this case, MCI-201 6 also attenuated the decrement of ACh level. These results suggest that improvement by MCI-2016 of behavioral impairment observed in the animals treated with scopolamine, hypoxia or ischemia may be, at least partly, attributed to the amelioration of decreased ACh level in the brain.

Effects of Bifemelane Hydrochloride (MCI-2016) on Acetylcholine and Norepinephrine Release from Cortical Slices of Bilaterally Carotid-Artery-Ligated Mongolian Gerbils

Effects of bifemelane hydrochloride (MCI-2016) on acetylcholine (ACh) and norepinephrine (NE) release from cortical slices of bilaterally carotid-artery-ligated Mongolian gerbils were examined. ACh and NE release from cortical slices of Mongolian gerbils were increased 1 hr after the ligation of bilateral carotid arteries. Pretreatment of MCI-2016 (25 mg/kg, i.p.) attenuated the increase in the release of both neurotransmitters. These effects may participate in the protective effect of MCI-2016 on cerebral ischemia in Mongolian gerbils.

Effects of Bifemelane Hydrochloride (MCI-2016) on Acetylcholine Release from Cortical and Hippocampal Slices of Rats

Bifemelane hydrochloride (MCI-2016) increased high K+-evoked acetylcholine (ACh) release from cortical and hippocampal slices of rats. The increasing effect of MCI-2016 was abolished in the absence of Ca ion and by pretreatment of reserpine (2.5 mg/kg, i.p.). These results suggest that monoaminergic neurons may be related to the enhancement of ACh release by MCI-2016. High K+-evoked ACh release from cortical slices was significantly decreased during aging. The decrease in ACh release was ameliorated by pretreatment of MCI-2016 (30 mg/kg, i.p.).