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

Egashira, Toru; Takayama, Fusako; Yamanaka, Yasumitsu

doi:10.1254/jjp.72.57

Cited by 30 publications

(11 citation statements)

References 28 publications

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“…Some of the basic experimental studies showed that these effects might result from activation of the muscarinic cholinergic system (4,16,17) or from protective effects against glutamate cytotoxicity (5). The reduction of HSP70 level during ischemia has been reported to result from the protecting effects of bifemelane against ischemic brain injury (18,19).…”

Section: Discussionmentioning

confidence: 99%

A Novel Effect of Bifemelane, a Nootropic Drug, on Intracellular Ca2+ Levels in Rat Cerebral Astrocytes

et al. 2006

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Abstract. We investigated the effects of bifemelane, a nootropic drug, on the intracellular calcium concentration ([Ca 2+ ] i ) in rat cerebral astrocytes using a Ca 2+ imaging device. At concentrations of 10 -30 µM, bifemelane induced a slow onset and small increase in the [Ca 2+] i , while at higher concentrations (100 -300 µM), it induced a rapid transient increase in the [Ca 2+] i during administration and a second large increase was seen during drug washout. The first peak was observed in Ca 2+ -free medium, but its onset was significantly delayed, and no second peak was seen. Neither of these effects was seen in cells treated with thapsigargin, a specific inhibitor of endoplasmic reticulum Ca 2+-ATPase, in Ca 2+ -free medium. When thapsigargintreated astrocytes were returned to normal medium containing Ca 2+ (1.8 mM), the [Ca 2+ ] i increased significantly, and this effect was reversely inhibited by bifemelane. We conclude that bifemelane causes the first peak by stimulating release from intracellular Ca 2+ stores and the second by capacitive entry through store-operated Ca 2+ channels. Although the detail mechanisms of action of the drug are still unknown, bifemelane will be provided as a pharmacological tool for basic studies on astrocytes.

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Section: Discussionmentioning

confidence: 99%

A Novel Effect of Bifemelane, a Nootropic Drug, on Intracellular Ca2+ Levels in Rat Cerebral Astrocytes

et al. 2006

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“…Because the improvement by 2-pyrrolidinone was too small as a whole. There may be different mechanisms at the cholinergic basis for metabolites, as shown for aniracetam, such as presynaptic release of acetylcholine [Giovannini et al, 1993] and an increase of choline acetyltransferase activity [Egashira et al, 1996]. Further studies with these metabolites will be necessary to clarify the exact mechanisms.…”

Section: Improvement By Aniracetam and Its Metabolitesmentioning

confidence: 99%

“…It has been speculated that the improvement of learning and memory by aniracetam is based on the activation of central cholinergic pathways [Nakajima et al, 1986;Spignoli and Pepeu, 1987;Giovannini et al, 1993;Egashira et al, 1996]. Concerning the interaction with cholinergic receptors, it has been reported that aniracetam and its metabolites produced no significant inhibition on nonselective muscarinic receptor bindings up to a concentration of 1 mM [Nakajima et al, 1986] and on nicotinic and muscarinic M 1 and M 2 receptor binding up to 10 µM [ Martin and Haefely, 1993].…”

Section: Improvement By Aniracetam and Its Metabolitesmentioning

confidence: 99%

Scopolamine model of delirium in rats and reversal of the performance impairment by aniracetam

Nakamura¹,

Kurasawa²,

Tanaka³

1998

Drug Dev. Res.

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“…On the other hand, the close link between vascular dementia and Alzheimer's disease is gradually being discovered. 38) Previous studies have demonstrated that central cholinergic system is damaged by permanent 2VO rats [39][40][41] and stimulation of central cholinergic systems improves spatial memory deficits in 2VO rats. 42) So we selected tacrine as a reference drug in the behavior test.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Breviscapine on Ischemic Vascular Dementia in Rats

Xiong

Liu

Wang

et al. 2006

Biological & Pharmaceutical Bulletin

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With an increase of elderly population, aging-related diseases such as hypertension, arteriosclerosis and different forms of dementia are also increased. 1) One of these diseases is vascular dementia (VD). VD is a step-wise deterioration in intellectual powers that appear as different areas of the brain are damaged by loss of blood supply.2,3) The conventional concept of VD is that of multi-infarct dementia, 3,4) arising from chronic cerebral ischemia and various vascular changes in the brain.5) It is reported that the reduction in cerebral blood flow and abnormal energy metabolism occurred in chronic cerebral ischemia can induce the accumulation of NO and ROS which lead to neurons injury in selective, vulnerable regions of the brain, especially the hippocampus and cerebral cortex, accompanied by cognitive decline and some motor disorders. [6][7][8] In oriental medicine, many traditional Chinese drugs have been used clinically for treatment of ischemic cerebrovascular disease. 9) Breviscapine is extracted from the traditional Chinese drug Erigeron Breviscapus (vant.) Hand.-Mazz and mainly composed of Scutellarein, Plantaginin and Pyromeconic acid. 10,11) The injection preparation of breviscapine has been used in clinic to treat cardiovascular diseases, cerebral infarction and stroke in China. 3,10,11) The clinical reports suggested that the injection of breviscapine (0.5 mg/kg, i.v. gtt, qd, 15 d) possess neuroprotective action and improves learning and memory in cerebrovascular diseases.12,13) Although the curative effect of breviscapine in cerebral infarction and cerebral ischemia is obvious, there is no data available for this drug in treatment of VD. In this study, the effects of chronic treatment with breviscapine on the learning deficits, neuronal injury and antioxidative properties in VD rats were investigated. MATERIALS AND METHODS Animal Models and Drug AdministrationThe vascular dementia models were made from the male Wistar rats (6 weeks, 230Ϯ10 g), which were obtained from the Experimental Animals Center of Tongji Medical College, Huazhong University of Science and Technology. Wistar rats were subjected to permanent occlusion of bilateral common carotid arteries to induce chronic cerebral ischemia and mimic the VD models.14) The experimental protocols were approved by the Committee of Animal Care of Huazhong University of Science and Technology.The injection of breviscapine (Bre, Bath No. z5302066, China) was purchased from Kunming Long-Jin Pharmaceutical Co., Ltd. Tacrine (9-amino-1,2,3,4-tetrahydroacridine HCl), a reference drug for behavioral test, was purchased from Sigma (St. Louis, MO, U.S.A.) and dissolved in physiological saline. Fifteen days after surgery, the male Wistar rats were randomly divided into three groups, e.g., sham-operated group, model group, Bre-treated group and tacrine-treated group. The Bre-treated group was administered with breviscapine (2 mg/kg, i.p., equal 0.33 mg/kg adult dose, once a day). Tacrine was administered intraperitoneally at a dosage of 3 mg/kg. The sham-ope...

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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

Cited by 30 publications

References 28 publications

A Novel Effect of Bifemelane, a Nootropic Drug, on Intracellular Ca2+ Levels in Rat Cerebral Astrocytes

A Novel Effect of Bifemelane, a Nootropic Drug, on Intracellular Ca2+ Levels in Rat Cerebral Astrocytes

Scopolamine model of delirium in rats and reversal of the performance impairment by aniracetam

Protective Effects of Breviscapine on Ischemic Vascular Dementia in Rats

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