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

Abstract

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.

Pharmacological Characterization of DM232 (Unifiram) and DM235 (Sunifiram), New Potent Cognition Enhancers

“…Sunifiram and unifiram, administered 20 min before each daily acquisition training, were able to prevent scopolamine-induced memory impairment ( Fig. 3) (12,13).…”

“…A procognitive activity of sunifiram and unifiram was unmasked by using a social learning test, performed according to Mondadori et al (37). Unifiram and sunifiram exerted beneficial effects on cognitive performance in the social learning test by prolonging the time normally required by rats to delete mnemonic information (12,31).…”

“…Moreover, mice treated with unifiram and sunifiram at the same doses retained motor coordination in the rotating rod test [method of Kuribara et al (27)] (Table 1) (11). The spontaneous motility of mice, evaluated by the Animex apparatus, as well as the exploratory behavior, studied by the hole-board test, were normal after unifiram and sunifiram administration (12,13 …”

Cognition-Enhancing Drugs in Mild Cognitive Impairment (MCI) and Alzheimers Disease (AD): An Update [1]

“…The compounds did not show any procognitive activity in the passive avoidance (mouse) and Morris water maze tests (rats) when given alone, but contrasted the amnesing effect of scopolamine at doses as low as 0.001 mg/kg, a dose three orders of magnitude lower than piracetam. At the highest effective doses, they did not impair motor coordination (rotarod test) nor modified spontaneous motility (Animex apparatus and hole board test) [193,194].…”

Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings

“…Summarizing the results reported in our papers, where the interested scientists are addressed for details in methods and procedures [5][6][7][8]10,[12][13][14][15][16][17][18] , the following were the main findings: (1) Unifiram and Sunifiram antagonized memory disruption is produced not only by the muscarinic antagonist scopolamine but also by mecamylamine (nicotinic antagonist), baclofen (GABA agonist), clonidine (alpha-2 agonist), and NBQX (AMPA antagonist) 16,18 . The MEDs varied according to the amnestic drug and administration way.…”