The α-asarone/clofibrate hybrid compound, 2-methoxy-4-(2-propenyl) phenoxyacetic acid (MPPA), is endowed with neuroprotective and anticonvulsant potentialities

Nicole Pages, Pierre Maurois, Pierre Bac, Jean Jacques Vanden Eynde, Joaquín Tamariz, Fernando Labarrios, Germán Chamorro, Joseph Vamecq

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

2-methoxy-4-(2-propenyl)phenoxy acetic acid (MPPA) is a synthetic drug previously developed to mimic hypolipidemic activity and reduce side-effects of α-asarone, a vegetal extract used in traditional medicine to treat cardiovascular, neurological and other human disorders. MPPA was here evaluated in a battery of tests previously used to characterize anticonvulsant/ neuroprotective and toxic potential of α-asarone in mice. MPPA toxicity was limited and doses up to 100 mg/kg induced neither hypothermia, nor reduction of spontaneous locomotor activity nor failure in rotarod test. Dose-dependent potentiation of the pentobarbital-induced sleeping was, however, observed at doses higher than 12.5 mg/kg. Little or no protection was provided by MPPA against seizures induced by N-methyl-D-aspartate. Moderate protection against subcutaneous pentylenetetrazol- and picrotoxin-induced seizures in mice, along with potentiation of pentobarbital-induced sleep, suggested GABAergic mechanisms. In maximal electroshock-induced seizures, MPPA protected 20% tested mice at 30 mg/kg and shortened recovery phase in convulsing mice, suggesting some action on neuronal voltage-gated sodium channels. High efficacy of MPPA was further observed in magnesium-dependent audiogenic seizures test, a murine model responsive to a variety of anticonvulsant, neuroprotective and antioxidant compounds. In this test, 50% animals were protected by 10 mg/kg MPPA, highlighting strong brain protective potential. In vitro, MPPA exhibited a superoxide-scavenging capacity about two-fold higher than that of α-asarone. Taken as a whole, present data support that MPPA is less toxic and more brain protective than α-asarone, and represents a worthy emerging neuroprotective/anticonvulsant compound endowed with a large activity spectrum including antioxidant, neuroprotective-like, moderate pro-GABAergic and sodium blockade mechanisms.

Original languageEnglish
Pages (from-to)210-215
Number of pages6
JournalBiomedicine and Aging Pathology
Volume1
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • 2-Methoxy-4-(2-propenyl) phenoxyacetic acid
  • Anticonvulsant and antioxidant properties
  • Chemical
  • Clofibrate
  • Electrical and audiogenic seizure tests
  • Magnesium deficiency
  • Neuroprotective
  • α-asarone

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