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

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.

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
• 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
• 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
• 5 Komae H, Hayashi N. Palmitone and phytosterols from Neolitesea seriacea .  Phytochemistry. 1971;  10 53-4
• 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
• 7 Sharma R K. Phytosterols: Wide-spectrum antibacterial agents.  Bioorganic Chemistry. 1993;  21 49-60
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 16 Meldrum S B. Update and the mechanism of action of antiepileptic drugs.  Epilepsy. 1996;  (Suppl. 6) 37 S4 - -S11
• 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
• 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
• 19 Henriksen O. An overview of benzodiazepines in seizure management.  Epilepsia. 1998;  (Suppl. 1) 39 S2 - -S6
• 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