Amnesic Actions of Diazepam and Scopolamine in Man

Frumin, M. Jack; Herekar, Vilas R.; Jarvik, Murray E.

doi:10.1097/00000542-197610000-00010

Cited by 62 publications

(16 citation statements)

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“…For instance, scopolamine, a muscarinic receptor blocking drug, has been shown to impair memory (Safer and Allen 1971;Frumier et al 1976) whereas muscarinic agonists, such as oxotremorine or arecoline, and acetylcholinesterase inhibitots, such as physostimnine, facilitate cognitive processes in animals and humans (Baratti et al 1979;Christie et al 1981;Mohs et al 1985). Prompted by such observations, certain studies have suggested that a dysfunction of cholinergic neuronal transmission may be an important factor in causing cognitive or memory deficits, as observed in senile dementias (Johns et al 1983;Sims et al 1983).…”

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confidence: 99%

Effects of nootropic drugs in a scopolamine-induced amnesia model in mice

et al. 1988

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Scopolamine (3 mg/kg IP) given before an acquisition trial, reduced the retention of a one-trial passive avoidance "step through" response in mice. A single administration of cholinergic agonists such as oxotremorine, BM-5, or arecoline, antagonized this amnesic effect of scopolamine. A significant anti-amnesic effect was also found with nootropic drugs such as piracetam and ucb L059, whereas ucb L060 (the enantiomer of ucb L059), oxiracetam and rolziracetam were shown to be ineffective. Moreover, ucb L059, administered twice daily for 3 days, counteracted the amnesic effects of scopolamine completely, whereas ucb L060 was again inactive. The results demonstrate that: (a) this model of impaired cognition by scopolamine is able to discriminate between closely related chemical substances and even stereoisomers; and (b) nootropic drugs, such as ucb L059, are more effective after repeated rather than after acute administration.

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Effects of nootropic drugs in a scopolamine-induced amnesia model in mice

et al. 1988

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“…On the other hand, a blockade of the cholinergic system produces a disruption of memory functions. The administration of scopolamine, an unselective muscarinic ACh receptor antagonist, results in impaired learning and memory in humans [Frumier et al, 1976] and animals [Levin and Bowman 1986]. Animals treated with the M 1 selective antagonist pirenzepine and dicyclomine had impaired memory processes in various paradigms in both mice and rats [Caufield et al, 1983;Sala et al, 1991;Ghelardini et al, 1997].…”

Section: Discussionmentioning

confidence: 99%

The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats

Ghelardini

Galeotti

Gualtieri

et al. 2002

Drug Development Research

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The favorable pharmacological profile exhibited by piracetam stimulated the synthesis of related compounds potentially endowed with a higher nootropic potency. The antiamnesic and procognitive activity of DM232 (unifiram), a new compound structurally related to piracetam, was investigated. Mouse passive avoidance and rat Morris water maze and Social learning tests were employed. DM232 (0.001-1 mg kg À1 i.p. -0.01-0.1 1 mg kg À1 p.o.) prevented amnesia induced by scopolamine (1.5 mg kg À1 i.p.), mecamylamine (20 mg kg À1 i.p.), baclofen (2 mg kg À1 i.p.), and clonidine (0.125 mg kg À1 i.p.). Furthermore, The antiamnesic effect of the investigated compound was comparable to that exerted by well-known nootropic drugs such as piracetam (30-100 mg kg À1 i.p.), aniracetam (100 mg kg À1 p.o.), rolipram (30 mg kg À1 p.o.), and nicotine (5 mg kg À1 i.p). DM232 (0.1 mg kg À1 i.p.) was also able to prevent amnesia induced by scopolamine (0.8 mg kg À1 i.p.) in the rat Morris watermaze test. In the rat social learning test, DM232 (0.1 mg kg À1 i.p.) injected in adults rats reduced the duration of active exploration of the familiar partner in the second session of the test. DM232, similarly to piracetam, reduced the duration of hypnosis induced by pentobarbital. At the highest effective doses, the investigated compound did not impair motor coordination (rota rod test), nor modified spontaneous (Animex). These results indicate DM232 (unifiram) as a novel cognition enhancer, strictly related to piracetam-like compounds, able to ameliorate memory impairment at doses about 1,000 times lower than the most active available nootropic compounds. Drug Dev.

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“…Conversely, blockade of the cholinergic system disrupts memory functions. The administration of scopolamine, an unselective muscarinic ACh receptor antagonist, impairs learning and memory in humans (Frumier et al 1976) and animals (Levin and Bowman 1986). Mice or rats treated with the M 1 selective antagonists pirenzepine and dicyclomine show impaired memory processes in various paradigms (Caulfield 1993;Sala et al 1991;Ghelardini et al 1997).…”

Section: Discussionmentioning

confidence: 99%

DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer

Ghelardini

Galeotti

Gualtieri

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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DM235 (sunifiram), a new compound structurally related to piracetam, prevented the amnesia induced by scopolamine (1.5 mg kg -1 i.p.), after intraperitoneal (0.001-0.1 mg kg -1 ) or oral (0.01-0.1 mg kg -1 ) administration, as shown by a passive avoidance test in mice. The antiamnesic effect of DM235 was comparable to that of well-known nootropic drugs such as piracetam (30-100 mg kg -1 i.p.), aniracetam (100 mg kg -1 p.o.) or rolipram (30 mg kg -1 p.o.). DM235 also prevented mecamylamine (20 mg kg -1 i.p.)-, baclofen (2 mg kg -1 i.p.)-and clonidine (0.125 mg kg -1 i.p.)-induced amnesia in the same test. In the Morris water maze test with rats, scopolamine (0.8 mg kg -1 i.p.) inhibited the reduction of escape latency in both acquisition and retention/retraining tests. DM235 (0.1 mg kg -1 i.p.), 20 min before each daily acquisition training, prevented the scopolamine-induced memory impairment. DM235 (1 mg kg -1 i.p.) also reduced the duration of pentobarbitone-induced hypnosis in mice without modifying the induction time of hypnosis. At the highest effective doses, the investigated compound neither impaired motor coordination (rota-rod test), nor modified spontaneous motility and inspection activity (Animex and hole board tests).These results indicate that DM235, a compound structurally related to piracetam, is a novel nootropic endowed with the capability to prevent cognitive deficits at very low doses. Indeed, its potency is about 1,000 times higher than that of the most active piracetam-like compounds.

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Amnesic Actions of Diazepam and Scopolamine in Man

Cited by 62 publications

References 0 publications

Effects of nootropic drugs in a scopolamine-induced amnesia model in mice

Effects of nootropic drugs in a scopolamine-induced amnesia model in mice

The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats

DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer

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