Anticonvulsant properties and bio-guided isolation of palmitone from leaves of Annona diversifolia.
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.
González-Trujano
M E
ME
Facultad de Química, Departamento de Farmacia. Universidad Nacional Autónoma de México, México D. F., México.
Navarrete
A
A
Reyes
B
B
Cedillo-Portugal
E
E
Hong
E
E
D000818:Animals; D000927:Anticonvulsants / Q000302:isolation & purification* / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced*; D006838:Hydrocarbons / Q000302:isolation & purification* / Q000494:pharmacology; D007659:Ketones / Q000302:isolation & purification* / Q000494:pharmacology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole / Q000494:pharmacology / Q000633:toxicity*; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012018:Reflex / Q000187:drug effects
D000927:Anticonvulsants; D006838:Hydrocarbons; D007659:Ketones; C423862:palmitone; D010433:Pentylenetetrazole