Research Article Study on Action Mechanism of 1-(4-Methoxy-2-Methylphenyl)Piperazine (MMPP) in Acquisition, Formation, and Consolidation of Memory in Mice Andrés Navarrete, 1 * Francisco X. Flores-Machorro, 1 Ruth I. Téllez-Ballesteros, 1 Alejandro Alfaro-Romero, 1 José Luis Balderas, 1 and Adelfo Reyes 2 1 Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México D.F., 04510, México 2 Facultad de Estudios Superiores Zaragoza, Unidad Multidisciplinaria de Investigación Experimental, Universidad Nacional Autónoma de México, Batalla 5 de Mayo esquina Fuerte de Loreto, Ejército de Oriente, Iztapalapa, México D.F., 09230, México Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I-III Regulatory, Quality, Manufacturing Postmarketing Phase IV ABSTRACT 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 consoli- dation, of memory in short-term and long-term protocol via cholinergic, NMDA-glutamatergic, and 5-HT1A receptors. Drug Dev Res 75 : 59–67, 2014. © 2013 Wiley Periodicals, Inc. Key words: nootropics; passive avoidance; phenylpiperazines; 1-(4-methoxy-2-methylphenyl)piperazine INTRODUCTION Cognitive dysfunction occurs in age-related pathologies, head injury, and neurodegenerative dis- eases including Alzheimer’s disease (AD). The nootro- pics, a class of cognition enhancers, represented by piracetam, have been used to treat cognitive dysfunction in patients with a moderate AD [Turan et al., 1998] and are safe and well tolerated [Pinza et al., 1993]. However, *Correspondence to: Andrés Navarrete, Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510. México D.F., México. E-mail: anavarrt@servidor.unam.mx Received 8 May 2013; Accepted 10 July 2013 Published online in Wiley Online Library (wileyonlinelibrary .com). DOI: 10.1002/ddr.21094 DRUG DEVELOPMENT RESEARCH 75 : 59–67 (2014) DDR © 2013 Wiley Periodicals, Inc.