Effects of Bifemelane Hydrochloride (MCI-2016) on Experimental Amnesia (Passive Avoidance Failure) in Rodents

Tobe, Akihiro; Yamaguchi, Taro; Nagai, R; Egawa, Mitsuo

doi:10.1254/jjp.39.153

Cited by 20 publications

(2 citation statements)

References 16 publications

(8 reference statements)

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“…In addition, noradrenaline re-uptake inhibition (Egawa et al., 1983) and monoamine oxidase inhibition (Naoi et al, 1988) have been described. It shows antiamnestic effects in rats and mice ( Ogawa et al, 1988a;Tobe et al, 1985) and elicits transcallosal responses in rats (Okuyama and Aihara, 1988). Bifemelane significantly inhibits the ischemia-induced depletion of acetylcholine in cerebral cortex, hippocampus and striatum of gerbils (Ogawa et al, 1988b).…”

Section: Cerebrai Metabolie Enhaneers (Fig 8)mentioning

confidence: 99%

The Families of Cognition Enhancers

Fröstl¹,

Maitre²

1989

Pharmacopsychiatry

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An attempt has been made to classify the numerous drugs used to treat cognition deficits according to their chemical structures and to their main physiological effects. Particular emphasis has been given to the following families: Piracetam-type, Co-dergocrine-type and vincamine-type compounds; cholinergic agents, psychostimulants, vasodilators, antianoxic agents, peptides, growth factors and gangliosides. Compounds described in the scientific literature and in patents are presented. Reference has been made to preclinical and clinical studies (973 quotations from original articles, 100 quotations of reviews and books).

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Section: Cerebrai Metabolie Enhaneers (Fig 8)mentioning

confidence: 99%

The Families of Cognition Enhancers

Fröstl¹,

Maitre²

1989

Pharmacopsychiatry

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“…From these results, bifemelane might cause an improvement of muscarinic re ceptors impaired in the hippocampus of SAM P/8. Recently, it has been reported that bifemelane hydrochloride suppressed the de crease in ACh concentration in the cerebral cortex and hippocampus of ischemic gerbils (10), the decrease in [3H]QNB binding in the hippocampus of aging rats, and decreases in learning and memory activities of scopolamine treated rats (11). Furthermore, bifemelane hydrochloride augments the long-term poten tiation in guinea pig hippocampal slices (12) through possible activation of protein kinase C (13), but the effect of this drug is inhibited by scopolamine.…”

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confidence: 99%

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

1991

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ABSTRACT-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.Senescence-accelerated prone mouse (SAM P/8), a murine model of accelerating aging, shows an earlier onset (about 8 months after birth) and irreversible advancement of senes cence manifested by the following signs and lesions: a loss of activity, alopecia and lack of hair glossiness, skin coarseness, periophthal mic lesions, a short life span, and systemic senile amyloidosis (1). SAM-P/8 shows an age-related deterioration of learning ability: a significant avoidance deficit in the passive avoidance task and prolongation of perfor mance time in the multiple-T maze task, com pared with control mouse, senescence-acceler ated resistant mouse (SAM-R/1) (2). Thus, SAM-P/8 may prove to be a pertinent model for studying the mechanisms related to the memory deficit seen in senile humans.Recent neurochemical investigations on pa tients with Alzheimer's disease (AD) and senile dementia of the Alzheimer's type (SDAT) have demonstrated cholinergic dys functions in the cerebral cortex and hippocam pus (3, 4): a decrease in muscarinic receptor density and marked reductions in the activity of choline acetyltransferase and/or acetylcho linesterase. In humans, moreover, inhibition of central cholinergic neurotransmission by treatment of scopolamine results in losses of memory and cognition that are similar to those in patients with AD and/or SDAT. In mice, scopolamine also induced the dysfunc tion, of learning and memory.Bifemelane hydrochloride, 4-(o-benzylphenoxy) N-methyl-butylamine hydrochloride, is a clini cally effective nootropic used in Japan for the treatment of the decrease in cognitive and emotional disturbances related to cerebro vascular disease. This drug improves scopola mine-induced memory deficits in rats (5) and enhances ACh release evoked by high potas sium (6). These results suggest the possible in volvement of the cerebral cholinergic system in the effects of bifemelane hydrochloride. We here examined the effects of single and re peated administration of bifemelane hydro chloride on specific [3H]QNB binding in the cerebral cortex and hippocampus of SAM-P/8, and we compared the binding parameters be tween SAM-P/8 and SAM-R/1 at 9 months

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