Abstracts

Currently available antiepileptic drugs (AEDs) are synthetic molecules with certain negative properties, which limit their utility and complicate patient management. It is generally estimated that up to 30% of patients diagnosed with epilepsy are refractory to available AED treatment. In this instance, the plant kingdom is undoubtedly a valuable source for the development of better and safer drugs for the treatment of epilepsy.
Nutmeg, the dried kernel of [italic]Myristica fragrans[/italic] Houtt (Myristicaceae), has been used for the treatment of epilepsy in traditional medicine. Previous reports have indicted that the pharmacological activity of nutmeg mainly exists in its volatile oil fraction. Volatile oil of nutmeg (nutmeg oil) was tested for its effects in maximal electroshock (MES), subcutaneous pentylenetetrazole (PTZ), strychnine (STN), bicuculline (BIC) and picrotoxin (PIC) seizure tests. At least three doses of nutmeg oil (50-300 [micro]l/kg) were tested against each seizure tests. Safety profile of nutmeg oil was established by determining its acute toxicity and acute neurotoxicity. Nutmeg oil was found to possess significant anticonvulsant activity against hind limb tonic extension in MES test. It also showed dose dependent anticonvulsant activity against different patterns of PTZ-induced seizures. It delayed the onset of hind limb tonic extensor jerks induced by STN. It showed both pro- and anticonvulsant effects against PTZ, BIC and PIC induced clonic seizures. Nutmeg oil didn[rsquo]t induce motor impairment when tested up to 600 [micro]l/kg in inverted screen acute neurotoxicity test. Furthermore, its HD[sub]50[/sub] (1265 [micro]l/kg) i.e. dose at which 50% of the animals lose their righting reflex and LD[sub]50[/sub] (2150 [micro]l/kg) values are much higher than its anticonvulsant doses (50-300 [micro]l/kg). Our results indicate nutmeg oil possesses anticonvulsant effect against generalized tonic clonic seizures. Moreover, potentiation and inhibition of clonic seizure activity can be due to the presence of both pro- and anticonvulsant compounds as well as dual activity. We conclude that nutmeg oil has higher margin of safety when tested in animal models of epilepsy and contains compounds that can be promising candidates of anticonvulsant drug development. (Supported by an Institutional grant from H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.)