PHYTOTHERAPY RESEARCH

Phytother. Res. 23, 153 –158 (2009)

Published online 9 December 2008 in Wiley InterScience
ANTICONVULSANT ACTIVITIES OF NUTMEG OIL 153
(www.interscience.wiley.com) DOI: 10.1002/ptr.2548

Anticonvulsant Activities of Nutmeg Oil of

Myristica fragrans

Abdul Wahab1,2,3*, Rizwan Ul Haq1,3, Aftab Ahmed1, Rafeeq Alam Khan2 and Mohsin Raza4
1
Section of Pharmacology, International Center for Chemical Sciences, H.E.J. Research Institute of Chemistry, University of
Karachi, Pakistan
2
Department of Pharmacology, Faculty of Pharmacy, University of Karachi, Pakistan
3
Institute of Neurophysiology, Charite-Universitatsmedizin Berlin, Germany
4
Applied Neuroscience Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran

The purpose of this study was to investigate the anticonvulsant activity of the volatile oil of nutmeg, the dried
seed kernel of Myristica fragrans Houtt, using well-established animal seizure models and to evaluate its potential
for acute toxicity and acute neurotoxicity. The volatile oil of nutmeg (nutmeg oil) was tested for its effects in
maximal electroshock, subcutaneous pentylenetetrazole, strychnine and bicuculline seizure tests. All the experi-
ments were performed at the time of peak effect of nutmeg oil. Nutmeg oil showed a rapid onset of action and short
duration of anticonvulsant effect. It was found to possess significant anticonvulsant activity against electroshock-
induced hind limb tonic extension. It exhibited dose dependent anticonvulsant activity against pentylenetetrazole-
induced tonic seizures. It delayed the onset of hind limb tonic extensor jerks induced by strychnine. It was
anticonvulsant at lower doses, whereas weak proconvulsant at a higher dose against pentylenetetrazole and
bicuculline induced clonic seizures. Nutmeg oil was found to possess wide therapeutic margin, as it did not
induce motor impairment when tested up to 600 µL/kg in the inverted screen acute neurotoxicity test. Further-
more, the LD50 (2150 µL/kg) value was much higher than its anticonvulsant doses (50–300 µL/kg). The results
indicate that nutmeg oil may be effective against grand mal and partial seizures, as it prevents seizure spread
in a set of established animal models. Slight potentiation of clonic seizure activity limits its use for the
treatment of myoclonic and absence seizures. Copyright © 2008 John Wiley & Sons, Ltd.

Keywords: epilepsy; anticonvulsant; Myristica fragrans; nutmeg oil; seizure; acute toxicity.

Medicinal plants have played and continue to play

INTRODUCTION
Epilepsy is one of the most common serious neurologi-
cal disorders. Around 50 million people in the world have
epilepsy and approximately 5% of the general popula-
tion experience at least one seizure (excluding febrile
seizures) during their lifespan (Bell and Sander, 2001).
Currently available antiepileptic drugs (AEDs) are syn-
thetic molecules that exert serious adverse effects, terato-
genicity and withdrawal symptoms. Pharmacotherapy
of epilepsy with available AEDs is symptomatic as these
drugs inhibit seizures and do not cure the underlying
disease process in the brain (Schmidt, 2002). It is gener-
ally estimated that up to 30% of patients are refractory
to conventional AED treatment. Moreover, refractory
epilepsy is associated with increased morbidity, social
isolation, dependent behavior, low rates of marriage,
unemployment, overall reduced quality of life and a
heavy burden on society (Arroyo et al., 2002). There is
thus a need for the development of better and safer
AEDs with improved clinical profiles.
* Correspondence to: Abdul Wahab, Institute of Neurophysiology, Charite-
Universitats-Medizin, Tucholskystrasse 10117, Berlin, Germany.
E-mail: abdul.wahab@charite.de
Contract/grant sponsor: H.E.J. Research Institute of Chemistry, Interna-
tional Center for Chemical Sciences, University of Karachi, Pakistan.
Copyright © 2008 John Wiley & Sons, Ltd.
Copyright © 2008 John Wiley & Sons, Ltd.
an invaluable role in the drug discovery process (Abelson,
1990; Heinrich, 2000). Plant extracts can be an impor-
tant source for the development of better and safer
drugs for the treatment of epilepsy. Several plants that
were reputed to possess antiepileptic properties in dif-
ferent folklore cultures have been found to exhibit anti-
convulsant activities in different animal models (Raza
et al., 2000).
Nutmeg, the dried seed kernel of Myristica fragrans
Houtt (Myristicaceae), has been used for the treatment
of epilepsy in traditional medicines of different countries
(Joshi, 2000; Mhaskar et al., 2000; Anonymous, 2002).
The pharmacological activity of nutmeg mainly exists
in its volatile oil fraction (Farnsworth, 1968; Kalbhen,
1971). Chemical analysis of the sample of volatile oil
of nutmeg (nutmeg oil) that was used for this study
indicates the presence of 37 constituents representing
99.3% of the total of nutmeg oil (Atta-ur-Rahman
et al., 2000), the percentage of major and most impor-
tant constituents were terpinen-4-ol (31.3), γ-terpinene
(7.8), myristicin (7.1), p-cymene (6.5), α-terpineol (5.2),
α-pinene (4.9), β-pinene (4.6), elemicin (4.8), α-terpinene
(3.5), limonene (3.2), methyleugenol (0.8), eugenol (0.2),
trans-methylisoeugenol (0.1) and linalool (0.4).
The objective of the present study was to assess the
anticonvulsant profile of nutmeg oil at the time of its
peak anticonvulsant effect using different animal sei-
zure models. For this purpose its effects in the maximal
Phytother. Res.Received 2 July(2009)
23, 153 –158 2007
Revised 14 February
DOI: 2008
10.1002/ptr
Accepted 17 February 2008
154 A. WAHAB ET AL.
electroshock seizure (MES) test, and pentylenetetrazole
(PTZ), bicuculline (BIC) and strychnine (STN) seizure
tests were investigated. The toxic potential of nutmeg
oil was investigated by determining its acute toxicity
and acute neurotoxicity.
MATERIALS AND METHODS
Plant material and isolation of nutmeg essential oil.
The dried kernels of the ripe seeds of Myristica fragrans
(nutmeg) locally known as ‘Jaifal’, with their peculiar
fragrance, were obtained from the herbal medicine store
and were identified by Dr Tahir Ali, Department of
Botany, University of Karachi where a voucher specimen
was deposited.
The extraction of nutmeg oil from the dried kernels
of ripe seeds was carried out by hydro-distillation,
using a Clevenger-type apparatus. The dried kernels
produced 2.28% of volatile oil within 8 h.
Experimental animals. Studies were carried out on NMRI
(Naval Medical Research Institute, USA) male mice
weighing 20–30 g, obtained from the animal house
facility of the Section of Pharmacology, H.E.J. Research
Institute of Chemistry, University of Karachi. Animals
were kept in groups of 5–6 in plastic cages and pro-
vided standard 12 h light/dark cycle beginning at 8 a.m.
Standard food and water were available ad libitum. All
experiments for anticonvulsant activity were carried
out between 8 a.m. and 1 p.m. Each animal was used
only once. All animals were treated in accordance
with ethical principles and regulations specified by the
Animal Care and Use Committee of our Institution.
Chemicals. Pentylenetetrazole (PTZ), bicuculline (BIC),
strychnine (STN) and polyethylene glycol 400 were
purchased from Sigma Chemical Company (St Louis, MO,
USA). Sodium valproate and phenytoin sodium were
received as gifts from Abbott Laboratories and Adamjee
Pharmaceuticals (Pakistan) Ltd, respectively. Nutmeg
oil was dissolved in polyethylene glycol 400, which was
diluted in water at a ratio of 30:70; this dilution has no
effect on seizure threshold (Loscher et al., 1990). PTZ,
STN, sodium valproate and phenytoin sodium were
dissolved in normal saline, whereas BIC was dissolved
in saline slightly acidified with 0.1 N HCl and was used
within 60 min after preparation. All the solutions used
were freshly made on the day of testing and administered
to a final volume of 0.1 mL/10 g body weight of mice.
Time course of anticonvulsant activity of nutmeg oil.
PTZ was administered subcutaneously (s.c.) at a dose
of 100 mg/kg in mice. At this dose the control animals
exhibited five different types of seizure patterns: (1) one
or more generalized myoclonic body twitch, (2) threshold
seizure (it is defined as an episode of continuous clonic
spasms without loss of righting reflex lasting for at least
5 s), (3) generalized clonic seizure with loss of righting
reflex, (4) loss of righting reflex with tonic fore limb
seizure, (5) loss of righting reflex with tonic fore and
hind limb seizure. The time course of anticonvulsant
action of nutmeg oil was determined by administering
an appropriate intraperitoneal (i.p.) dose (200 µL/kg) of
nutmeg oil 5, 30 and 60 min before s.c. administration
Copyright © 2008 John Wiley & Sons, Ltd.
of PTZ (100 mg/kg) to three groups of eight animals
each. The time at which the greatest response was
observed was taken as the time of peak effect (TPE)
(Loscher et al., 1991). The time of maximum protection
from PTZ-induced seizures was then used for quantifi-
cation of anticonvulsant potencies in all the seizure
models.
Anticonvulsant testing on seizure models
PTZ seizure test. In order to quantify the anticonvulsant
effect of nutmeg oil in this model, three doses of nutmeg
oil were administered to groups of 10 mice and then
PTZ (100 mg/kg, s.c.) was injected at the previously
determined TPE (5 min, as indicated in the Results) of
nutmeg oil. Animals were observed for 1 h for the pres-
ence or absence of different types of seizure patterns
(Loscher et al., 1991; Raza et al., 2001a, 2001b). Valproic
acid (450 mg/kg i.p.) was used as a positive control and
administered 30 min before the PTZ injection.
Maximal electroshock seizure (MES) test. The MES test
was carried out via transauricular electrodes by means
of a stimulator (ECT unit, model 7801, Ugo Basile, Varese,
Italy) using a fixed supramaximal current of 50 mA with
a frequency of 60 Hz for 0.2 s. This stimulus was suffi-
cient to produce hind limb tonic extension in control
animals. The animals were administered three doses
of nutmeg oil (50, 100 and 200 µL/kg) i.p. in groups of
10 to calculate the anticonvulsant effect. Nutmeg oil
was tested in this test at the previously determined TPE
(5 min, as indicated in the Results) in the PTZ test.
Animals not displaying electroshock induced hind
limb tonic extension phase were considered protected
(White et al., 1998). Phenytoin (20 mg/kg) was used as
a positive control and administered i.p. 30 min before
the electroshock.
STN and BIC seizure tests. The STN and BIC tests
were carried out by s.c. administration of 1.2 mg/kg of
STN and 2.7 mg/kg of BIC, respectively, at the pre-
determined TPE (5 min) of nutmeg oil in the PTZ test.
Three doses of nutmeg oil were tested in each seizure
test. Nutmeg oil was tested for its ability to block clonic
seizure in the BIC seizure test and hind limb tonic
extensor jerks in the STN test (White et al., 1998).
Latency to hind limb tonic extensor jerk and mortality
were also calculated in the STN test. The latency to
hind limb tonic extensor jerk or mortality is defined
as the interval between the end of the STN-injection
and the occurrence of first episode of hind limb tonic
extensor jerk or death.
Toxicity profile
Acute neurotoxicity. The potential of testing material
to induce motor impairment was determined using an
inverted screen acute neurotoxicity test (Coughenour
et al., 1977). Briefly, the apparatus consisted of 13 cm
square screen of 0.6 cm wire mesh supported by metal
bars. Mice were individually placed on a wire mesh
screen elevated a few cm above the ground, then
the screen was inverted through an arc of 180°. Mice
unable to climb at an upright position within 1 min were
Phytother. Res. 23, 153 –158 (2009)
DOI: 10.1002/ptr
 ANTICONVULSANT ACTIVITIES OF NUTMEG OIL
rated as failures. Animals were pretested on the appa-
ratus on the day preceding the experiment, and those
failing the task were not used for the subsequent drug
test. Testing was carried out at 5, 30, 60 and 120 min
following i.p. administration of different doses of
nutmeg oil in groups of 10 mice.
LD50. The dose that caused death in 50% of animals
within 24 h (LD50) was calculated using the method
described by Lorke (1983). Briefly, nutmeg oil at a dose
of 10, 100 and 1000 µL/kg was administered i.p. to
groups of three mice each. Based on the results of
mortality in each group after 24 h, four more mice were
administered different doses of nutmeg oil in order
to obtain the least and most toxic values and the LD50
was calculated by the geometric mean of these values
(Lorke, 1983).
HD50. The HD50, i.e. dose at which 50% of animals loss
their righting reflex, was calculated after i.p. adminis-
tration of different doses of nutmeg oil. The loss of
righting reflex was assessed on the tabletop by placing
the animals in a supine position at 5, 10, 60 and 120 min
after administration of nutmeg oil (Swinyard and
Kupferberg, 1985).
Statistics. The latency to seizures and death in the STN
test were expressed as mean ± SEM. A difference between
the control and experimental groups were tested for
statistical significance by Student’s t-test. Difference was
considered significance when p < 0.05 and < 0.01. The
LD50 value of nutmeg oil was determined by Lorke’s (1983)
method, which requires a few animals to give median
values and has been proved valid for its accuracy (van
Noordwijk et al., 1988). The HD50 value was calculated
by graphic presentation method.
RESULTS
Anticonvulsant activity
Time course of anticonvulsant activity of nutmeg oil.
As illustrated in Fig. 1, nutmeg oil 200 µL/kg exhibited
Figure 1. Time course of anticonvulsant effect of nutmeg oil
(200 µl/kg) against different patterns of PTZ-induced seizures
(n = 8/group). GBT, one or more generalized myoclonic body
twitch; TS, threshold seizure; GSR, generalized clonic seizure
with loss of righting reflex; LFS, loss of righting reflex with
tonic fore limb seizure; LHS, loss of righting reflex with tonic
fore and hind limb seizure.
Copyright © 2008 John Wiley & Sons, Ltd.
155
a rapid onset of anticonvulsant action and a short dura-
tion of effect against PTZ-induced seizures with TPE at
5 min and duration of action less than 1 h, as no protec-
tion was evident at 1 h.
PTZ seizure test. Nutmeg oil showed dose-related effects
against different patterns of PTZ-induced seizures. As
illustrated in Fig. 2, 200 µL/kg of nutmeg oil provided
30% protection from myoclonic twitch, whereas 100 and
300 µL/kg were ineffective. 100 and 200 µL/kg of nutmeg
oil provided 70% and 100% protection, respectively,
from threshold seizure and generalized clonic seizures
with loss of the righting reflex, whereas 300 µL/kg of
nutmeg oil was not only ineffective but also slightly
increased the frequency and severity of threshold seizure.
Furthermore, 100 and 200 µL/kg afforded complete
protection, whereas 300 µL/kg provided 60% and 70%
protection from loss of the righting reflex with tonic
fore limb and tonic fore and hind limb seizures respec-
tively (Fig. 2). In valproic acid treated animals, only
myoclonic twitches were observed in 40% of animals
(data not shown in the graph).
MES test. Nutmeg oil showed dose-dependent anti-
convulsant activity against electroshock induced hind
limb tonic extension phase. As shown in Fig. 3, nutmeg
oil, at the dose of 50 and 100 µL/kg, provided 60% and
90% protection, respectively, and at a dose of 200 µL/
kg afforded complete protection against hind limb tonic
extension phase. Phenytoin provided complete protec-
tion in this test (Fig. 3).
STN and BIC seizure tests. Nutmeg oil offered no pro-
tection but showed dose-related effect in increasing
the latency to STN-induced first tonic extensor jerk and
death. 100 µL/kg dose of nutmeg oil had no effect, whereas
200 and 300 µL/kg significantly increased the latency to
first tonic extensor jerk and death (Fig. 4A, B).
100 and 200 µL/kg of nutmeg oil protected 62.5%
and 50% of mice, respectively, from BIC-induced clonic
seizures, whereas 300 µL/kg of nutmeg oil did not pro-
vide any protection and slightly increased the frequency
and severity of clonic seizures. Valproic acid (450 mg/
kg i.p.) showed complete protection from BIC-induced
clonic seizures (n = 8/group) (Fig. 5).
Figure 2. Anticonvulsant effects of nutmeg oil on different pat-
terns of PTZ-induced seizures, 5 min after i.p. administration to
mice (n = 10/group). GBT, one or more generalized myoclonic
body twitch; TS, theshold seizure; GSR, generalized clonic sei-
zure with loss of righting reflex; LFS, loss of righting reflex with
tonic fore limb seizure; LHS, loss of righting reflex with tonic
fore and hind limb seizure.
Phytother. Res. 23, 153 –158 (2009)
DOI: 10.1002/ptr
156 A. WAHAB ET AL.
Figure 3. Anticonvulsant effect of nutmeg oil against hind limb
tonic extension phase in MES test, 5 min after i.p. administra-
tion. Phenytoin (20 mg/kg i.p.) was used as positive control
(n = 10/group).
Figure 4. (A) Effect of nutmeg oil on latency to strychnine (STN)-
induced hind limb tonic extensor jerks. (B) Effect of nutmeg oil
on latency to strychnine (STN)-induced mortality. n = 8/group,
* p < 0.05, ** p < 0.01 (student’s t-test).
Figure 5. Anticonvulsant effect of nutmeg oil against bicuculline
(BIC)-induced clonic seizure. Valproic acid (450 mg/kg i.p.) was
used as positive control (n = 8/group).
Copyright © 2008 John Wiley & Sons, Ltd.
Toxicity profile
Acute neurotoxicity. In inverted screen acute neurotoxi-
city test, nutmeg oil up to 600 µL/kg at time intervals
of 5, 30, 60 and 120 min did not impair the ability of
mice to climb inverted screen within 1 min duration.
LD50. The LD50 of nutmeg oil was 2150 µL/kg/24 h. All
the animals lost their righting reflex followed by clonic
seizures before death. This clonus was accompanied by
periods of running (running-bouncing clonus).
HD50. The HD50 of nutmeg oil was calculated to be
1265 µL/kg. The animals lost their righting reflex within
10 min, while they recovered their righting reflex within
60 min. In control animals (vehicle injected) the reflex
was instantaneous in that they immediately rolled over
into their normal upright position.
DISCUSSION
The PTZ test is widely used in initial stages of anti-
convulsant drug development to evaluate the ability of
test materials to raise the seizure threshold for excita-
tion of neural tissue. Test materials that inhibit PTZ-
induced threshold seizure may be used for the treatment
of human generalized myoclonic and absence seizures
(Swinyard and Kupferberg, 1985). The time course study
of nutmeg oil in PTZ test indicates a rapid onset of
action and short duration of anticonvulsant effect. Nut-
meg oil showed dose-related activity against different
patterns of PTZ-induced seizures. At lower doses (100
and 200 µL/kg), it showed significant anticonvulsant
activity against PTZ-induced threshold seizure and
generalized clonic seizure with loss of righting reflex.
At a higher dose (300 µL/kg), it showed a weak pro-
convulsant effect; this potentiation of threshold seizure
activity at higher dose limits its use for the treatment of
myoclonic and absence seizures in humans. The results
of nutmeg oil at a dose of 200 µL/kg in PTZ seizure
test are comparable to the standard broad-spectrum
anticonvulsant drug valproic acid that provided signifi-
cant protection against myoclonic twitch and showed
complete protection against all other seizure patterns.
The activity of nutmeg oil in PTZ test indicates the
presence of anticonvulsant compound(s) that may pro-
duce an effect by either inhibiting low threshold T-type
Ca++ currents or enhancing GABAA receptor mediated
inhibition, as PTZ-induced seizures can be blocked
by standard drugs that reduce T-type Ca++ currents,
such as ethosuximide, and drugs that enhance GABAA
receptor mediated inhibition, such as benzodiazepines,
phenobarbital and valproic acid (White, 1999).
Nutmeg oil showed dose-dependent anticonvulsant
activity against hind limb tonic extension phase in the
MES test. It provided 100% protection from hind limb
tonic extension at the dose of 200 µL/kg. The MES test
is used to evaluate the ability of a substance to prevent
seizure spread through neural tissue and is considered
as a standard model for grand mal seizure (generalized
tonic clonic seizures) (Loscher and Schmidt, 1988). Most
standard drugs effective against grand mal seizures are
also effective against partial seizures. MES-induced hind
limb tonic extension is blocked by standard drugs that
Phytother. Res. 23, 153 –158 (2009)
DOI: 10.1002/ptr
 ANTICONVULSANT ACTIVITIES OF NUTMEG OIL
inhibit voltage dependent Na+ channels, such as phenytoin,
carbamazepine, lamotrigine and valproic acid (White,
1999). Thus the activity of nutmeg oil in MES test may
be due to the presence of compounds that block Na+ chan-
nel. The strong inhibitory effect of nutmeg oil against
MES-induced hind limb tonic extension suggests that
it may be useful for the treatment of grand mal and
partial seizures. The significant anticonvulsant activity
of nutmeg oil (100% protection at 200 µL/kg) against
loss of righting reflex with tonic fore limb and tonic
fore and hind limb seizures in PTZ test also demon-
strates that this oil is capable of preventing the spread
of seizure and may be good candidate to be used for
the treatment of grand mal and partial seizures.
STN is a competitive glycine receptor antagonist
(Rajendra et al., 1997). Nutmeg oil showed a dose-
dependent anticonvulsant effect in the STN test by
increasing the latency to first tonic extensor jerk and
death. This further demonstrates the ability of nutmeg
oil to prevent the spread of seizure.
BIC is a reversible GABAA receptor antagonist (Curtis
et al., 1970). At lower doses (100 and 200 µL/kg),
nutmeg oil provided significant protection from clonic
seizures, whereas at higher dose (300 µL/kg), it showed
weak proconvulsant effect by slightly increasing the
frequency and severity of clonic seizures. The activity
of nutmeg oil in BIC test may be due to the presence
of compound that mediates its effect through GABAA
related mechanism, as BIC-induced seizures can be
blocked by standard drugs that enhance GABAA receptor
mediated inhibition, such as barbiturates, benzodiaze-
pines, valproic acid, vigabatrin and gabapentin (Loscher
and Schmidt, 1994).
The present results confirm the traditional use of
nutmeg oil for the treatment of epilepsy and suggest
it may be effective for the treatment of grand mal
and partial seizures in human, the weak proconvulsant
activity of nutmeg oil for clonic seizures at a higher
dose does not reduce its effectiveness since some stand-
ard AEDs (phenytoin, carbamazepine, oxcarbazepine)
effective against grand mal and partial seizures
potentiate the myoclonic and absence seizures at cer-
tain doses in laboratory animals and humans (Rumke,
1967; Pranzatelli and Nadi, 1995; Genton, 2000; Gelisse
et al., 2004).
In the initial stages of anticonvulsant identification
and quantification particular attention is directed to
adverse effects, especially those characterized by neuro-
logical deficits (White et al., 1998). The inverted screen
acute neurotoxicity test, developed by Coughenour
et al. (1977), is used to quantify the effect of testing
material on motor function (Loscher and Schmidt,
1988). In this test, compounds with ataxic properties
produce dose-dependent increases in screen test fail-
ures, whereas other classes of drugs (e.g. psychomotor
stimulants) do not. Nutmeg oil did not induce motor
impairment and ataxia when tested up to 600 µL/kg
in the inverted screen acute neurotoxicity test. This
indicates that nutmeg oil has a wide therapeutic
margin.
Copyright © 2008 John Wiley & Sons, Ltd.
157
The dose of test material at which 50% of animals
exhibit a loss of the righting reflex (HD50) is also a matter
of concern in the initial stages of anticonvulsant identi-
fication and quantification (Swinyard and Kupferberg,
1985). The HD50 of nutmeg oil was calculated to be
1265 µL/kg; hence the anticonvulsant doses of nutmeg
oil are much smaller than its HD50. This effect of nutmeg
oil may be due to the presence of constituents that enhance
GABA-mediated inhibition, as standard AEDs benzo-
diazepines and phenobarbital cause loss of righting
reflex in high doses (Swinyard et al., 1986).
Previous studies on the constituents of nutmeg oil reveal
the presence of CNS active compounds with multiple
mechanisms of action. Pinene analogues, the major
constituents of nutmeg oil, have been reported for their
anticonvulsant activities in audiogenic seizure suscepti-
ble mouse (Consroe et al., 1981). Terpineol, another
major constituent of nutmeg oil, induced the dose-
dependent and reversible blockade of the compound
action potential propagation of the rat sciatic nerve
(Moreira et al., 2001). Although linalool and eugenol
derivatives were present in small amounts but they may
give additive or synergistic action to other anticon-
vulsant constituents of nutmeg oil, as linalool has been
reported to provide protection against PTZ, electro-
shock, NMDA and quinolinic acid induced and possess
activity in PTZ-kindling model seizures (Elisabetsky
et al., 1995, 1999; Brum et al., 2001). Similarly, eugenol
derivatives have also been found to possess activity in
the PTZ seizure test (Dallmeier and Carlini, 1981). The
weak proconvulsant activity of nutmeg oil for clonic
seizures may be due to the myristicin and elemicin,
which are metabolized in vivo into amphetamine-like
compounds (Shulgin, 1966; Kalbhen, 1971; Braun and
Kalbhen, 1973). Another major constituent of nutmeg
oil terpinene-4-ol, has not been studied extensively for
its CNS effects, and therefore may contribute to the
CNS activity of nutmeg oil.
In conclusion, the present data indicate that nutmeg
oil is active in multiple seizure models, and may be efficient
against grand mal and partial seizures, as it prevents
seizure spread by inhibiting the tonic seizure activity in
well-established animal seizure models. The slight poten-
tiation of clonic seizure activity limits its use for the
treatment of myoclonic and absence seizures. Nutmeg
oil has an acceptable safety profile as evidenced by acute
toxicity and acute neurotoxicity tests. Although the
exact mechanism(s) of action of nutmeg oil needs more
investigation the overall the effects of nutmeg oil in
seizure models indicates that it mediates a part of its
effect through GABA mediated neurotransmission and
by interaction with neuronal sodium channels.
Acknowledgements
This work was supported by an institutional grant from H.E.J. Research
Institute of Chemistry, International Center for Chemical Sciences,
University of Karachi, Pakistan. The authors would like to thank Dr
Mesbah Alam of Institute of Neurophysiology, Charité Universitä-
tsmedizin Berlin, Germany for critical comments on manuscript.
Phytother. Res. 23, 153 –158 (2009)
DOI: 10.1002/ptr
158 A. WAHAB ET AL.
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DOI: 10.1002/ptr