Study on action mechanism of 1-(4-methoxy-2-methylphenyl)piperazine (MMPP) in acquisition, formation, and consolidation of memory in mice.

In the present study, the mechanism of action of MMPP (1-(4-methoxy-2-methylphenyl) piperazine) in the acquisition (pretraining administration), formation (posttraining administration), and consolidation (pretest administration) of memory was assessed in the passive avoidance test using a short- and long-term memory protocol in mice. MMPP modified avoidance in the acquisition and formation of memory protocols but not in the consolidation protocol. Scopolamine (0.1 mg/kg i.p.), dizocilpine (0.003 mg/kg i.p.), and buspirone (0.1 mg/kg i.p.) completely inhibited MMPP-induced effects on memory acquisition and partially inhibited memory formation in the short-term but not long-term paradigm. This suggested that cholinergic, N-methyl-D-aspartate (NMDA) and 5-hydroxytryptamine-1A (5-HT1A ) receptors were implicated in the MMPP-induced improvements in memory. The sedative, anxiolytic, motor impairment, myorelaxant, and anticonvulsive (pentylenetetrazole-induced seizures) properties of MMPP were also assessed with the compound only showing a nondose-dependent myorelaxation. These results suggest that MMPP can enhance acquisition and formation, but not consolidation, of memory in short-term and long-term protocol via cholinergic, NMDA-glutamatergic, and 5-HT1A receptors.

Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.

Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2-oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and (R,S)-3 were obtained in good yields in only two steps starting from methyl DL-phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor-coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one derivatives constitute a new kind of nootropic compounds.

Phytotoxins from Hofmeisteria schaffneri: isolation and synthesis of 2'-(2' '-hydroxy-4' '-methylphenyl)-2'-oxoethyl acetate1.

Activity-directed fractionation of a CH(2)Cl(2)-MeOH (1:1) extract of Hofmeisteria schaffneri led to the isolation of a new phytotoxin characterized as 2'-(2' '-hydroxy-4' '-methylphenyl)-2'-oxoethyl acetate and designated the trivial name of hofmeisterin (1). In addition, the known compounds beta-carotene, euparin, and 3',4',4a',9a'-tetrahydro-6,7'-dimethylspiro[benzofuran-3(2H),2'-pyrano[2,3-b]benzofuran]-2,4a'-diol (2) were obtained. The identification of the isolates was accomplished by spectroscopic methods. The structure of 1 was unequivocally confirmed by synthesis. The methyl derivative 1a was also synthesized following the same strategy. Compounds 1 and 2 inhibited radicle growth of Amaranthus hypochondriacus (IC(50) = 3.2 x 10(-4) and 1.2 x 10(-5) M, respectively) and significantly inhibited activation of the calmodulin (CaM)-dependent enzyme cAMP phosphodiesterase (PDE) with IC(50) values of 4.4 and 4.22 microM, respectively.