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Planta Med 2001; 67(2): 136-141
DOI: 10.1055/s-2001-11504
Original Paper

© Georg Thieme Verlag Stuttgart · New York

Anticonvulsant Properties and Bio-Guided Isolation of Palmitone from Leaves of Annona diversifolia 1

María Eva González-Trujano2, 3, 4 , Andrés Navarrete2,*, Benito Reyes5 , Ernestina Cedillo-Portugal6 , Enrique Hong4
  • 1 Taken in part from the Ph. D. research work of M.E. González-Trujano
  • 2 Facultad de Química, Departamento de Farmacia. Universidad Nacional Autónoma de México, México D. F., México
  • 3 Instituto Mexicano de Psiquiatría, México, D. F., México
  • 4 Sección de Terapéutica Experimental. Departamento de Farmacología y Toxicología. CINVESTAV IPN, México, D.F., México
  • 5 Laboratorio de Productos Naturales. Area de Química. Universidad Autónoma Chapingo, México
  • 6 Area de Biología. Universidad Autónoma Chapingo, México
Further Information

Publication History

February 11, 2000

July 2, 2000

Publication Date:
31 December 2001 (online)

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Abstract

The activity-guided fractionation of the ethanol extract of leaves of Annona diversifolia Saff., led to the isolation of palmitone (16-hentriacontanone) as the only anticonvulsant active compound. This aliphatic ketone was highly effective to diminish pentylenetetrazole (PTZ)-induced clonic-tonic seizures and toxicity. Also, it produced a prolongation of the latency for onset of seizures and a reduction of the death rate produced by 4-aminopyridine (4-AP) and bicuculline (BIC). However, it was inactive to inhibit the kainic acid (KA)- and strychnine (STC)-induced seizures. Palmitone did not produce motor incoordination and loss of righting reflex which are used as signs of neurological impairment. Palmitone (ED50 = 1.85 mg/kg) proved to be a more potent antiepileptic drug against the PTZ-induced seizures than etosuximide (ED50 = 59.6 mg/kg), sodium valproate (ED50 = 63 mg/kg), and carbamazepine (ED50 > 300 mg/kg) and it was only four-fold less potent than diazepam (ED50 = 0.48 mg/kg). The pharmacological profile of palmitone suggests that this compound could be acting on the GABAergic inhibitory system.

Key words

Annona diversifolia - Annonaceae - 16-hentriacontanone - anticonvulsant - epilepsy - Mexican traditional medicine

References

  • 1 Ruiz S E, Morett A L. Las Anonas en el México Prehispánico. Chapingo, Estado de México; Memorias Congreso Internacional de Annonáceas 12 - 14 Noviembre, 1997: 169-86
  • 2 González-Trujano M E, Navarrete A, Reyes B, Hong E. Some pharmacological effects of the ethanol extract of leaves of Annona diversifolia on the central nervous system in mice.  Phytotherapy Research. 1998;  12 600-2
    CrossrefPubMedSearch in Google Scholar
  • 3 Pudles J, Lederer S. Sur L'Isolement et a Constitution Chimique de L'Acide Coryno-mycolénique et de Deux Cétones des Lipides du Bacille diphtérique.  Bulletin de la Societé de Chimique Biologique. 1954;  36 759-77
    PubMedSearch in Google Scholar
  • 4 Hayashi N, Komae H. Isolation and identification of palmitone from the leaves of Lauraceae plants (Cinnamomun camphora Sieb., Neolitsea sericea Koidz, Lindera umbellata Thumb.)  Journal of the Indian Chemical Society. 1971;  48 288
    PubMedSearch in Google Scholar
  • 5 Komae H, Hayashi N. Palmitone and phytosterols from Neolitesea seriacea .  Phytochemistry. 1971;  10 53-4
    PubMedSearch in Google Scholar
  • 6 Behari J, Sharma R K. Isolation of 16-hentriacontanone, alcohols and sterols from the leaves of Annona squamosa .  Journal of the Indian Chemical Society. 1986;  63 255-6
    PubMedSearch in Google Scholar
  • 7 Sharma R K. Phytosterols: Wide-spectrum antibacterial agents.  Bioorganic Chemistry. 1993;  21 49-60
    CrossrefPubMedSearch in Google Scholar
  • 8 Boissier J R, Simon P, Zaczinska M, Fichelle J. Etude Psychopharmacologique Experimentale d'une Nouvelle Substance Psychotrope, 1a 2-ethyl-amino-5-chloro-4-phényl-4,3,1bezoxacine.  Thérapie. 1972;  27 325-38
    PubMedSearch in Google Scholar
  • 9 Porsolt R, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants.  Archives Internationales de Pharmacodynamie et de Therapie. 1977;  229 327-35
    PubMedSearch in Google Scholar
  • 10 Vajdi M, Nawar W W, Merritt C Jr. GC/MS analysis of some long chaine esters, ketones and propanediol diesters.  Journal of the American Oil Chemist's Society. 1981;  58 106-10
    PubMedSearch in Google Scholar
  • 11 Macdonald R L, Barker J L. Pentylenetetrazole and penicillin are selective antagonist of GABA-mediated post-synaptic inhibition in cultured mammalian neurons.  Nature. 1977;  267 720-2
    CrossrefPubMedSearch in Google Scholar
  • 12 Rehavi M, Skolnick P, Paul S M. Effects of tetrazole derivatives on [3H]-diazepam binding. In vitro: correlation with convulsant potency.  European Journal of Pharmacology. 1982;  78 353-6
    CrossrefPubMedSearch in Google Scholar
  • 13 Marescaux C, Vergnes M, Depaulis S. Genetic absence epilepsy in rats from Strasbourg. A review.  Journal of Neural Transmission. General Section. 1992;  Suppl. 35 37-69
    PubMedSearch in Google Scholar
  • 14 Curtis D R, Duggan A W, Johston  AR. Bicuculline an antagonist of GABA and synaptic inhibition in the spinal cord.  Brain Research. 1971;  32 88-96
    PubMedSearch in Google Scholar
  • 15 Coulter D A, Hugenard J R, Prince D A. Differential effects of petit mal anticonvulsants and convulsants on thalamic neurons: Calcium current reduction.  British Journal of Pharmacology. 1990;  100 800-6
    PubMedSearch in Google Scholar
  • 16 Meldrum S B. Update and the mechanism of action of antiepileptic drugs.  Epilepsy. 1996;  (Suppl. 6) 37 S4 - -S11
    PubMedSearch in Google Scholar
  • 17 Keane P E, Simiand J, Mendes E, Santucci V, Morre M. The effects of analogues of valproic acid on seizures induced by pentylenetetrazol and GABA content in brain of mice.  Neuropharmacology. 1983;  22 875-9
    CrossrefPubMedSearch in Google Scholar
  • 18 Sher P K, Study R E, Mazzetta J, Barker J L, Nelson P G. Depression of benzodiazepine binding and diazepam potentiation of GABA-mediated inhibition after chronic exposure of spinal cord cultures to diazepam.  Brain Research. 1983;  268 171-6
    CrossrefPubMedSearch in Google Scholar
  • 19 Henriksen O. An overview of benzodiazepines in seizure management.  Epilepsia. 1998;  (Suppl. 1) 39 S2 - -S6
    PubMedSearch in Google Scholar
  • 20 Gouemo P N, Koudogbo B, Tchivounda H P, Nguema A, Etova M M. Effects of ethanol extract of Annona muricata on pentylenetetrazol-induced convulsive seizures in mice.  Phytotherapy Research. 1997;  11 243-5
    CrossrefPubMedSearch in Google Scholar

Dr. Andrés Navarrete

Facultad de Química Conjunto E,

Departamento de Farmacia

Universidad Nacional Autónoma de México

Coyoacán 04510

México D.F.

México

Email: anavarrt@servidor.unam.mx.

Fax: (5) 6 22 53 29

Phone: (5) 6 22 52 91