Oxiracetam prevents electroshock-induced decrease in brain acetylcholine and amnesia

Spignoli, G.; Pepeu, Giancarlo

doi:10.1016/0014-2999(86)90055-5

Cited by 63 publications

(15 citation statements)

References 14 publications

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“…At lower doses, oxiracetam en hances neuronal transmission (in vitro dose: 10-6 -10-7 M) (6) and facilitates memory and learning in mice (in vivo dose: 10-50 mg/kg) (1). At higher doses, moderate and transient cerebral impairment is improved (in vivo dose: 50 300 mg/kg) (2,4). Furthermore, in the present study, we found that oxiracetam mini mized severe ischemic metabolic damage (in vivo dose: 400-800 mg/kg).…”

Section: Physiological Variablessupporting

confidence: 62%

The Effects of Oxiracetam (CT-848) on Local Cerebral Glucose Utilization after Focal Cerebral Ischemia in Rats.

et al. 1992

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-The effects of oxiracetam on the reduction of brain metabolism induced by focal cerebral ischemia were investigated by measuring local cerebral glucose uti lization (LCGU) in rats 24 hr after left middle cerebral artery occlusion. Focal cere bral ischemia reduced LCGU in the entire ipsilateral cortex, the greatest reduction being in the lateral parts of the frontoparietal cortex. LCGU was slightly reduced in the contralateral cortex; this reduction was considered to be caused by diaschisis. Ox iracetam was administered intraperitoneally for 3 days prior to middle cerebral artery occlusion. In the ipsilateral cortex, LCGU reduction was minimized in the ischemic center areas by oxiracetam at a dose of 400 mg/kg and in more extensive areas, by a dose of 800 mg/kg. Moreover, oxiracetam at a dose of 800 mg/kg enhanced metabo lism impaired by diaschisis in the caudal areas of the contralateral cortex. These find ings suggest that oxiracetam minimizes the reduction of brain function induced by ischemia and may therefore be useful in the treatment of cerebrovascular disease.The pharmacological actions of oxiracetam are similar to those of other pyrrolidone de rivatives, including piracetam, aniracetam and pramiracetam. Oxiracetam and other pyrroli done derivatives have been reported to im prove memory and learning ability in normal animals (1) and to prevent amnesia and the decrease in brain acetylcholine level induced by scopolamine and electroshock in rats (2 4). Oxiracetam and piracetam stimulate high affinity choline uptake in the rat hippocampus (5). Thus, the effects of pyrrolidone deriva tives may be related to the enhancement of brain cholinergic mechanisms. In addition, ox iracetam and other pyrrolidone derivatives have been shown to augment hippocampal long-term potentiation in rats (6) and guinea pigs (7,8). These investigations suggest that pyrrolidone derivatives enhance cerebral func tion in normal brain and protect it in impaired brain. Since we have recently found that ox iracetam protects rats and mice against cere bral hypoxia, we expected to find that ox iracetam had protective effects against cere bral ischemia in this experiment.Focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion (9) is a use ful model (9, 10) for studying ischemic brain damage, as well as cerebral blood flow (11, 12), energy metabolism (13), and neurotrans mitters (14,15). Sokoloff (16) showed that cerebral functional activity was closely coupled to energy metabolism, especially glucose con sumption. In this study, we investigated

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Section: Physiological Variablessupporting

confidence: 62%

The Effects of Oxiracetam (CT-848) on Local Cerebral Glucose Utilization after Focal Cerebral Ischemia in Rats.

et al. 1992

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“…ECS has been reported to alter central nervous system functions. A decrease in acetylcholine (ACh) levels (Spignoli and Pepeu, 1986) and an increase in acetylcholinesterase activity (Appleyard et al, 1987), inhibition of GABA synthesis and increase in noradrenaline and serotonin release (Green et al, 1987a(Green et al, , 1987b have been reported.…”

Section: Discussionmentioning

confidence: 98%

“…Active avoidance learning acquisition and its retention were tested by the method of Spignoli et al (1986). The apparatus used was the conventional shuttle avoidance box (Techno, India), which consisted of two grid-floor compartments (29 Â 29 Â 25 cm each) separated by a plexiglass transparent partition with a single opening (14 Â 17 cm) and a buzzer.…”

Section: Methodsmentioning

confidence: 99%

Brain neurotransmitter receptor binding and nootropic studies on Indian Hypericum perforatum Linn.

Kumar

Khanna

Seth

et al. 2002

Phytotherapy Research

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The high affinity binding sites for serotonin and benzodiazepine in the frontal cortex, for dopamine in the striatum and muscarinic cholinergic receptors in the hippocampus were investigated in the brains of Charles Foster rats treated for 3 days. Transfer latency on elevated plus maze (TL), passive and active avoidance behaviour (PA and AA) and electroconvulsive shock (ECS) induced amnesia were also studied. Pilot studies indicated that single dose administration of Indian Hypericum perforatum (IHp) had little or no acute behavioural effects and hence the extract of IHp was administered orally at two dose levels (100 and 200 mg/kg, p.o.) once daily for 3 consecutive days, while piracetam (500 mg/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard nootropic agent. Control rats were treated with an equal volume of vehicle (0.3% carboxymethyl cellulose). The results indicate that IHp treatment caused a significant decrease in the binding of [3H] spiroperone (DA-D2 receptor) to the striatum and an increase in the binding of [3H] ketanserin (5-HT2A receptor) and [3H] flunitrazepam (BDZ receptor) to the frontal cortex in rats. Preliminary pharmacological studies with IHp extract indicate the presence of two major behavioural actions, namely, antidepressant and anxiolytic. The present findings tend to elucidate the mechanism of earlier observations, the downregulation of the dopamine D2 receptor being consonant with anxiolytic and the upregulation of 5-HT2A and BDZ receptors being consonant with antidepressant activity. Piracetam when given alone, shortened the TL on days 1, 2 and 9 day and also antagonized the amnesic effects of ECS on the TL significantly, whereas IHp antagonized the amnesia produced by ECS. IHp had no significant effect per se on the retention of the PA in rats but produced a significant reversal of ECS induced PA retention deficit. Piracetam showed a significant facilitatory effect per se on PA retention and also reversed the ECS induced impaired PA retention. In the AA test, piracetam facilitated the acquisition and retention of AA in rats but IHp had no effect per se. Both the doses of IHp and piracetam significantly attenuated the ECS induced impaired retention of AA. These results indicate a possible nootropic action of IHp in amnesic animals, which was comparable qualitatively to piracetam.

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“…Oxiracetam (4-hydroxy-2-oxo-1-pyrolidine acetamide) (1) is a neurochemically active drug that shows inotropic properties, especially in elderly patients [1]. The molecular structure of oxiracetam shows that it is a simple polar lactam of low molecular mass.…”

Section: Introductionmentioning

confidence: 99%

Molecular modelling studies and the chromatographic behaviour of oxiracetam and some closely related molecules

Camilleri¹,

Murphy²,

Saunders³

et al. 1991

J Computer-Aided Mol Des

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Oxiracetam prevents electroshock-induced decrease in brain acetylcholine and amnesia

Cited by 63 publications

References 14 publications

The Effects of Oxiracetam (CT-848) on Local Cerebral Glucose Utilization after Focal Cerebral Ischemia in Rats.

The Effects of Oxiracetam (CT-848) on Local Cerebral Glucose Utilization after Focal Cerebral Ischemia in Rats.

Brain neurotransmitter receptor binding and nootropic studies on Indian Hypericum perforatum Linn.

Molecular modelling studies and the chromatographic behaviour of oxiracetam and some closely related molecules

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