Journal of Ethnopharmacology 76 (2001) 145– 150

www.elsevier.com/locate/jethpharm

Anticonvulsant properties of the methanolic extract of Cyperus

articulatus (Cyperaceae)
E. Ngo Bum a,*, M. Schmutz b, C. Meyer b, A. Rakotonirina c, M. Bopelet c,
C. Portet b, A. Jeker b, S.V. Rakotonirina c, H.R. Olpe b, P. Herrling b
a
Département des Sciences Biologiques, Faculté des Sciences, Uni6ersité de Ngaoundéré, B.P. 454 Ngaoundere, Cameroon
b
No6artis Pharma Ltd., Research, CH-4002 Basel, Switzerland
c
Département de Biologie et Physiologie Animale, Faculté des Sciences, B.P. 812 Uni6ersité de Yaoundé, Yaounde, Cameroon

Received 29 July 2000; received in revised form 13 December 2000; accepted 12 January 2001

Abstract

The methanolic extract of rhizomes of Cyperus articulatus, a plant used in traditional medicine in Africa and Latin America for
many diseases, possesses anticonvulsant activity in mice. This extract protected mice against maximal electroshock (MES)- and
pentylenetetrazol (PTZ)-induced seizures. It also delayed the onset of seizures induced by isonicotinic acid hydrazide and strongly
antagonized N-methyl-D-aspartate-induced turning behavior. The ED50 for protection against seizures was 306 (154– 541) mg/kg
intraperitoneally (i.p.) for the PTZ test and 1005 (797–1200) mg/kg i.p. for the MES test. The ED50 of methanolic extract against
N-methyl-D-aspartate-induced turning behavior was 875 (623– 1123) mg/kg i.p. C. articulatus L. methanolic extract protected 54%
of mice from seizures induced by strychnine at the dose of 1000 mg/kg i.p. but had no or a moderate effect only against
picrotoxin- or bicuculline-induced seizures. With these effects, the rhizome of C. articulatus L. possesses anticonvulsant properties
in animals that might explain its use as a traditional medicine for epilepsy in Africa. © 2001 Elsevier Science Ireland Ltd. All
rights reserved.

Keywords: Epilepsy; Anticonvulsant; Methanolic extract; Seizures; Cyperus articulatus L.

1. Introduction (decoction) is drunk by patients with epilepsy. The chem-

Cyperus articulatus L. is a marshland plant found in
many countries in Africa and Latin America (Hutchin-
son et al., 1972; Schultes and Raffauf, 1990). In
Cameroon, Central Africa Republic, Gabon and Sene-
gal the decoction of its rhizome is used to treat many
diseases such as malaria, toothache, headache, migraine
(Bouquet, 1969; Adjanohoun et al., 1984; Burkill,
1985). According to the pro6ider ofthe plant, the decoc-
tion of the rhizomes of C. articulatus is used to treat
epilepsy. In the traditional medicine, the rhizomes powder
is boiled in water for at least 30 min. The supernatant
Abbre6iations: AMPA – L-amino-3-hydroxy-5methyl-isoxazole-4-
propionic acid; Carba – Carbamazyepine; Clonaz – Clonazepam;
INH – Isonicotinic acid hydrazide; ME – Methanolic extract; MES
– Maximal electroshock; STR – Strychnine; NMDA – N-methyl-D-
aspartate; PTZ – Pentylenetetrazol.
* Corresponding author. Tel.: + 237-252-773; fax: + 237-252-599.
E-mail address: boum@cna-assur.com (E.N. Bum).
ical characterization of rhizomes of C. articulatus L.
shows the presence of flavonoids, saponins, cathechins,
triterpenes, sesquiterpenes and ketones (Neville and
Nigam, 1968; Nyasse, 1987; Ngo Bum, 1991). As some
of the diseases treated with C. articulatus L. (migraines,
headaches and according to a personal communication
also epilepsy) concern the nervous system, some phar-
macological work has been done to define its interac-
tion with this system. These studies showed that
decoction of rhizomes of C. articulatus L. possesses
depressant activity in the central nervous system. The
decoction of rhizomes reduced the spontaneous motor
activity in mice and showed sedative properties since it
significantly facilitated and prolonged diazepam- or
sodium thiopental- induced sleep in mice (Ngo Bum et
al., 1991). Further studies showed a selective dose-de-
pendent inhibition of N-methyl-D-aspartate (NMDA),
but not L-amino-3 hydroxy-5-methyl-isoxazole-4-prpi-
onic acid (AMPA) receptor-mediated neurotransmis-

0378-8741/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 7 8 - 8 7 4 1 ( 0 1 ) 0 0 1 9 2 - 1
146 E.N. Bum et al. / Journal of Ethnopharmacology 76 (2001) 145–150
sion in the rat cortical wedge preparation (Ngo Bum et
al., 1996). Since NMDA receptor antagonists have anti-
convulsant properties in vivo (Schmutz et al., 1990) and
the extract of rhizomes of C. articulatus L. is used in
traditional medicine to also treat epilepsy, we decided
Fig. 1. Effect of ME on NMDA-induced turning behavior in mice: (a)
shows the percentage of protected animals. The ME significantly
protected mice against NMDA-induced turning behavior in a dose-
dependent manner. The ED50 of the ME was 875 (623 –1123) mg/kg
i.p. nE10 per dose, ***PB 0.001 (Fisher exact test: two tail) and (b)
shows the time (s) of the latency of seizures in non-protected animals.
At 500 mg/kg i.p., the ME provided a slight increase in the time to
the onset of the turning behavior in mice. The doses of the ME are in
mg/kg. The control groups were treated with CGP37849 3 mg/kg
(CGP) or DMSO, 40% (DMSO). nE 8 per dose, (ME 2000, n =1).
**PB0.01 (Correction for multiple t-test by Bonferroni method).
Fig. 2. Effect of the ME on PTZ-induced clonic seizures in mice: The
figure represents the percentage of animal protected by each treat-
ment. The ME dose dependently protected mice against seizures
induced by PTZ. ED50 =306 (154 – 541) mg/kg i.p. The doses of the
ME are in mg/kg. The control groups were treated with clonazepam
0.1 mg/kg (Clonaz) or DMSO, 40% (DMSO). n E 10 per dose,
*PB 0.05, **PB0.01, ***PB 0.001 (Fisher exact test: two tail).
Fig. 3. Effect of the ME on INH-induced seizures in mice: The
duration of the latency of seizures induced by INH in the presence of
ME in mice increased in a dose dependent manner. The doses of the
ME are in mg/kg. The control groups were treated with diazepam 10
mg/kg or DMSO, 40% (DMSO). Latency in s expressed as means
9 SD, n E 10 per dose, **PB 0.01, ***PB 0.001 (Correction for
multiple t-test by Bonferroni method).
to test the effects of this extract in animal models of
epilepsy.
2. Methodology
2.1. Plant material
The plant specimens of C. articulatus L. used in these
studies were collected in Cameroon. A voucher speci-
men (Rakotonirina 002, reference 1256/HNC) was au-
thentifled and deposited in the National Herbarium of
Cameroon. The extract of C. articulatus used in these
studies was obtained according to a method described
 E.N. Bum et al. / Journal of Ethnopharmacology 76 (2001) 145–150 147

Table 1
Effect of the methanolic extract on STR-induced tonic seizures in micea

Compounds Clonazepam DMSO 40% ME 100 ME 200 ME 500 ME 1000 ME 2000

Doses (mg/kg) 3 100 200 500 1000 2000

Latency of seizures (s) 4779139* 2879 140 317 9179 372 9135 406 9 119** 388 9133 411 9134**
Percentage of protection 78.3 27.6 20.0 0 10.0 53.8 35.0

a
Latency in s, means 9 SD (nE10). *PB0.01, **
PB0.05. (Correction for multiple t-test by Bonferroni method).

Table 2
Effect of the methanolic extract on BIC and PIC-induced seizures in micea

Compounds BIC 2.7 mg/kg (i.p.) PIC 7.5 mg/kg (i.p.)

Time of onset of seizures (s) Percentage of protected mice Latency of seizures (s)

DMSO 40% 2609104 0 192 984

ME 2000 mg/kg 3079 148 0 240 989
Clonazepam 0.4 mg/kg Not tested 80 270 9 42

a
Latency in s, means 9 SD (nE10).

previously (Ngo Bum et al., 1996). In short: the dried ‘positive control group’ receiving 3 mg/kg CGP 37849
rhizomes of C. articulatus were ground. The powder of NMDA antagonist that normally provide 100% protec-
the plant was extracted with ethyl acetate (in order to tion (Schmutz et al., 1990).
study ethyl acetate extract, because ethyl acetate can
extract components that are a little beat less polar than
2.3.2. Pentylenetetrazol test
the methanol ones) and the supernatant filtered. The
The method has been described previously (Schmutz
solid phase was extracted with methanol. The extract,
et al., 1990). In brief, clonic seizures were induced in
filtered and dried, constituted the methanolic extract
male mice by the i.p. injection of 70 mg/kg pentylenete-
(ME) that was tested in some models of epilepsy. The
trazol (PTZ). The protective effect of the ME was
ME was diluted in 40% DMSO (dimethyl sulfoxide) in
recorded. The time of onset of seizures in non-protected
distilled water and administered intraperitoneally (i.p.)
mice was also recorded. There were two control groups,
1 h before the test. The following doses of the ME were
used: 50, 100, 200, 500, 1000 and 2000 mg/kg.

2.2. Animals

Adult male mice (OF 1; Iffa Credo, Les Oncins,

France; 20–25 g; at least 10 per group) were used
throughout these studies. The animals were housed in
standard cages at 23°C on a 12 h light-dark cycle. They
were supplied with food and water ad libitum.

2.3. Anticon6ulsant tests

2.3.1. N-methyl-D -aspartate test

Mice were injected subcutaneously (s.c.) with
NMDA, 75 mg/kg, 1 h after administration of the
extract. They were observed for 30 mm. Animals that
did not exibit turning behavior within the 30 mm
observation period were declared protected. Turning
was characterized by two consecutive 360° cycles fulfi-
lled by the same animal. For the non-protected ani-
mals, the onset time of this behavior was recorded.
There were two control groups: one with placebo and a
Fig. 4. Effect of the ME on MES-induced tonic seizures in mice: The
figure represents the percentage of animals that did not exhibit
seizures induced by MES. The doses of the ME are in mg/kg. The
control groups received 30 mg/kg carbamazepine (Carba) or DMSO
40% (DMSO). n E10 per dose, ***PB 0.001 (Fisher exact test: two
tail).
148 E.N. Bum et al. / Journal of Ethnopharmacology 76 (2001) 145–150
one receiving placebo and a positive control group
receiving 0.1 mg/kg clonazepam.
2.3.3. Strychnine test
The method has been described previously (Lehmann
et al., 1988). In brief, strychnine (STR) convulsions
followed by death were induced in male mice by the i.p.
injection of 2.5 mg/kg STR nitrate. A protective effect
of the ME given i.p. 1 h prior to STR was recorded and
compared to the one of 3 mg/kg clonazepam. The
number of animals, which survived more than 10 min
served as criterion of protection. The time to onset of
death was recorded in non-protected mice.
2.3.4. Isonicotinic acid hydrazide (isoniazid; INH) test
Animals were injected i.p. with INH 250 mg/kg
(Bernasconi et al., 1988) 1 h after the administration of
the ME, and the time to onset of clonic or tonic
seizures was recorded. Data of the control group
(treated with placebo) were compared to data of the
group treated with the ME. The positive control group
received diazepam, 10 mg/kg orally (per os).
2.3.5. Bicuculline test
Animals were injected i.p. with bicuculline (BIC) 2.7
mg/kg (Masereel et al., 1998; Palmer et al., 1999) 1 h
after the administration of the ME. The time to onset
of clonic or tonic seizures was recorded in the control
group (treated with placebo) and in the group treated
with the ME.
2.3.6. Picrotoxin test
The method has been described previously (Lehmann
et al., 1988). In brief, clonic seizures were induced in
male mice by the i.p. injection of 7.5 mg/kg picrotoxin
(PIC). A protective effect of the extract against PIC-in-
duced clonic seizures was recorded. A 0.4 mg/kg dose
of clonazepam was used as positive control.
2.3.7. Maximal electroshock test
The method has been described previously (Schmutz
et al., 1990; Wamil et al., 1994). In brief, tonic convul-
sions of the hind extremities of mice were induced by
passing alternating electrical current (50 Hz, 18 mA, 0.2
s) through temporal electrodes. For each experiment
one group served as a negative control (placebo) and
one group as a positive control (carbamazepine, 30
mg/kg p.o.). The number of animals protected from
tonic hind limb extension seizure and the time spent in
this position were determined in each dose group.
2.4. Analysis of data
Three parameters were measured. The protection
against maximal electroshock (MES) and chemically
induced seizures that was expressed as percentage of
animals without seizures, the latency to the onset of
seizures and the time of tonic extension of hind extrem-
ities in MES. The ED50 values (dose at which 50% of
the animals are protected) and 95% confidence limits
were determined by using the SAS probit procedure
with Abbot’s correction. For the latency to the onset of
seizures and the time of tonic hind limb extension
seizure in the MES test, the mean values of the control
groups were compared to the mean values of the groups
treated with the extracts using the correction for multi-
ple t-test by Bonferroni method. The Fisher exact test
(two-tail) was used to compare percentage of protected
mice in each case. The doses of ME are in mg/kg.
2.5. Chemicals
PTZ, BIC, PIC, NMDA, STR, INH, carbamazepine
are from sigma chemical, USA; CGP 37849 from No6ar-
tis, Basle, Switzerland.
3. Results
3.1. Effect of the methanolic extract on
NMDA-induced turning beha6ior
The turning behavior induced by NMDA (75 mg/kg)
was antagonized by the dose of 3 mg/kg i.p. of the
NMDA antagonist CGP 37849 (Schmutz et al., 1990).
The ME also prevented mice from turning. This effect
was dose-dependent: 20%, 60% and 90% of the animals
did not show turning behavior at the doses of 500, 1000
and 2000 mg/kg i.p., respectively. At the highest dose,
the protection provided by the extract was better than
the one provided by CGP 37849. In non-protected
animals, the time of the onset of the turning behavior
was also delayed by the ME (control group: 10169290
s; ME 500 mg/kg: 14039283 s). The ED50 in protect-
ing animals against turning behavior was 875 (623–
1123) mg/kg i.p. (Fig. 1 a and b).
3.2. Effect of the methanolic extract on PTZ-induced
seizures
The ME dose-dependently protected animals against
clonic seizures induced by PTZ but did not delay the
onset of seizures in non-protected animals. At the dose
of 100 mg/kg i.p., the ME protected 40% of mice
against seizures. The dose of 2000 mg/kg provided
protection for 90% of mice. The ED50 was 306 (154–
541) mg/kg i.p. Fig. 2 shows the dose-response relation-
ship of the effect of the ME.
3.3. Effect of the methanolic extract on INH-induced
seizures
The effect of the ME was dose-dependent. It in-
creased the time to the onset of seizures from 38.896.1
 E.N. Bum et al. / Journal of Ethnopharmacology 76 (2001) 145–150
min to 48.89 10.6 min at the dose of 200 mg/kg ip.,
and from 38.896.l min to 71.2916.8 min at the dose
of 2000 mg/kg i.p. This is a 183% increase compared to
control. At this dose the ME was nearly as efficacious
as diazepam, 10 mg/kg (Fig. 3).
3.4. Effect of the methanolic extract on STR-induced
seizures and exitus
ME at the dose of 1000 mg/kg i.p. protected 54% of
mice from tonic seizures and death induced by STR 2.5
mg/kg, that is 69% of the effect of clonazepam, 3 mg/kg
(78% protection). The same dose only slightly but sig-
nificantly delayed the onset of the seizures from 4.8 mm
to 6.5 mm in non-protected animals (Table 1).
3.5. Effect of the methanolic extract on BIC- and
PIC-induced seizures
The ME at a dose of 2000 mg/kg did not possess a
significant effect against seizures induced by BIC and
PIC (Table 2).
3.6. Effects of the methanolic extract on MES-induced
seizures
The ME antagonized MES-induced seizures. The
doses of 1000 and 2000 mg/kg i.p. of ME protected
55% and 95% of mice, respectively. This effect was
comparable to that of carbamazepine (30 mg/kg), a
standard antiepileptic drug. The ED50 of the ME was
1005 (797–1200) mg/kg i.p. (Fig. 4).
3.7. Unwanted effects
Mice treated with 1000 and 2000 mg/kg i.p. of ME
showed ataxia 1 h after its administration. At lower
doses, no clear unwanted effects were observed.
4. Discussion and conclusion
The ME of rhizomes of C. articulatus L. contains at
least one component that antagonizes chemically and
electrically induced seizures in mice. The ME of C.
articulatus L. significantly protected mice against PTZ,
STR and MES-induced seizures. The respective ED50 s
were 306 (154–541) mg/kg i.p. for the PTZ and 1005
(797–1200) mg/kg i.p. for the MES test. In non-pro-
tected mice, the ME significantly delayed the onset of
seizures induced by STR and INH. Turning behavior
induced by NMDA in mice was dose-dependently an-
tagonized by ME. The ED50 in this test was 875 (623–
1123) mg/kg i.p. The ME had very modest effect on
BIC-induced seizures and no effect on PIC-induced
seizures. Among the tests used, the MES and PTZ tests
149
are of predictive relevance regarding the clinical spec-
trum of activity of experimental compounds (Rogawski
and Porter, 1990; Kupferberg and Schmutz, 1998). Be-
cause the MES and PTZ tests are assumed to identify
anticonvulsant drugs effective against generalized tonic-
clonici partial seizures and generalized clonic seizures,
respectively (Löscher and Schmidt, 1988; Rogawski and
Porter, 1990; De Deyn et al., 1992; Kupferberg and
Schmutz, 1998), the effect of the ME in these tests
could therefore suggest anticonvulsant efficacy against
the above mentioned seizures types in man. As PTZ
and INH have been shown to interact with the GABA
neurotransmitter and the GABA receptor complex
(Doctor et al., 1982; Löscher and Schmidt, 1988; De
Deyn et al., 1992), antagonism of PTZ- and INH-in-
duced seizures suggests that the extract of C. articulatus
L. might have effects on GABA-ergic neurotransmis-
sion. But these effects do not seem to be related to the
GABA or PIC sites of the GABA receptor complex (De
Deyn et al., 1992) because BIC- and PIC-induced
seizures were not significantly antagonized. It has been
shown previously that an extract of rhizhomes of C.
articulatus selectively antagonized NMDA receptor-me-
diated neurotransmission in rat cortical wedge in vitro
(Ngo Bum et al., 1996). These results are in accordance
with the present in vivo studies since ME dose-depen-
dently antagonized NMDA-induced turning behavior
in mice. The moderate antagonism of the ME in STR-
induced seizures suggests that additional mechanisms
might be involved. The multiplicity of putative mecha-
nisms of action and the broad spectrum of anticonvul-
sant activity of the ME might be due to the presence of
different active components in the ME interacting
simultaneously. These mechanisms and their contribu-
tion to the anticonvulsant properties of the ME will be
better understood once the active components in the
rhizome of C. articulatus are identified. Although, the
traditional medicine uses the decoction but not the ME to
treat epilepsy, the results of this study confirms the
presence of anticon6ulsant properties in the rhizomes of
C. articulatus. Comparison between the ME extract and
de decoction could be made after the study of the effects
of the decoction in the same animal models of epilepsy.
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