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Natural Anticonvulsants: A Review

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 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

ISSN 0974-3618 www.rjptonline.org

REVIEW ARTICLE
Natural Anticonvulsants: A Review
Surendra Nath Pandeya*, Rajeev Kumar and Ashish Kumar Pathak
Medicinal Chemistry Research Laboratory, Department of Pharmacy, Saroj Institute of Technology and
Management, Sultanpur Road, Lucknow, Pin-226002, U.P., India.
*Corresponding Author E-mail: snpande65@yahoo.co.in

ABSTRACT
Epilepsy is a neurological disorder affecting a large scale of the population, which accounts for about 1% of the world’s
burden of diseases. A large number of agents called antiepileptic drugs are available to treat various types of seizures with the
objective to reduce seizure frequency and severity within a framework of an acceptable level of side effects. There are
number of drugs available for treatment of epilepsy in modern therapy. But the major disadvantage being faced is their
chronic side effects. Treatment of epilepsy with herbal drugs as adjuvant seems to be more beneficial and is gaining more
popularity due to their fewer side effects. Herbal drugs are acting at target site having same mechanism of action as that of
synthetic drugs. There is still a need for new antiepileptic drugs (AEDs), may be derived from natural sources, as the clinical
efficacy tolerability, toxicity properties of existing synthetic AEDs may not be satisfactory. This review focuses on the use of
natural products for control of epilepsy.

KEYWORDS: Natural AEDs, Herbal anticonvulsants.

1-INTRODUCTION:
Epilepsy is a neurological disorder that affects a wide range of It has been observed that the presently available antiepileptic
people throughout the world1. Epilepsy has now become the drugs are unable to control seizures effectively in as many as
most serious brain disorder, which accounts for about 1% of 25% of the patients.As majority of antiepileptic drugs are
the world’s burden of diseases. Epilepsy is a neurological consumed life long, concomitant administration of other drugs
disorder characterized by excessive electrical discharge in predisposes to the risk of drug interaction (given in table-2).
brain, which cause seizures. The therapeutic strategy in
countering epilepsy involves reducing neuronal excitability The current therapeutic treatment of epilepsy with modern
through different mechanistic pathways given in figure. antiepileptic drugs (AEDs) is associated with side-effects,
dose-related and chronic toxicity, and teratogenic effects, and
Most therapeutics currently used in the treatment of epilepsy is approximately 30% of the patients continue to have seizures
either directed toward blocking voltage-gated sodium and with current AEDs therapy. The currently available synthetic
calcium channels or potentiating gamma amino butyric acid antiepileptic drugs provide seizure control in upto 70% patient
(GABA)-mediated neurotransmission, with little focus on with epilepsy , the remaining patient have refractory epilepsy.
voltage-gated potassium ion channels, despite these channels
having a major role in the control of all aspects of neuronal Thus there is still need to develop new drugs with greater
excitability. It is reported that functional impairment of clinical efficacy, tolerability minimal side effect, devoid of
potassium in channels, either by mutation or inhibition result in unfavorable drug interactions and better pharmacokinetic
4,5
epilepsy3. Incidence of epilepsy in developed countries is properties .
approximately 50 per 100,000 while that of developing country
is 100 per 100,000 (WHO, 2006). In many tropical countries 2-NATURAL PRODUCTS:
the incidence of epilepsy was estimated to be greater than 0.5% Traditional medicine involves the use of herbal medicine,
of a given population and is higher in male than female with a animal parts and minerals. However, herbal medicines are the
majority having their first attack before the age of twenty4. most widely used of the above three. Herbal medicines contain
A number of synthetic antiepileptic drugs are available in an active ingredient, aerial or underground parts of plants as
practice, however their effectiveness does not hold true with their petal or seeds materials or combinations thereof, whether
the entire range of population suffering from this disorder. The in the crude state or as plant preparations. Furthermore, about
conventional antiepileptic agents like phenytoin and sodium 80% of the world population is dependent (wholly or partially)
valporate carry with them several serious side effects notably on plant-based drugs (WHO, 1996)6.
neurotoxicity (given in table-1).
OH
Received on 08.06.2009 Modified on 03.08.2009
Accepted on 10.09.2009 © RJPT All right reserved
Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009; Page 670-679 Linalool
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 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

O O drugs. A detailed account from various plant derived product

OH are described in the given table (3).
O
O O
Mechanism through which plants act as anticonvulsant
N agents:
It was thought that epileptic drugs inhibit seizure by regulating
GABA mediated synaptic inhibition and /or by blocking post-
synaptic 5-HT receptors and /or by inhibiting serotonergic
cocaine Linoleic acid transmission44.

Bacopa monnieri:
On the other hand, the world health organization has estimated
The neuroprotective role of B.monnieri extract in alteration of
that perhaps 80% of the world’s population relies chiefly on
glutamate receptor binding and gene expression of NMDA R1
traditional medicine for primary health care needs. Moreover,
in hippocampus of temporal lobe epileptic rats were observed.
allopathic science may gain much from the study of such
The neuroprotective role of B.monnieri extract in alteration of
systems and important allopathic drugs like digitalis, quinine,
glutamate receptor binding and gene expression of NMDA R1
atropine and several others have originated from plant sources.
in hippocampus of temporal lobe epileptic rats were observed.
The discipline of Ayurveda (An alternative system of
In association with pilocarpine-induced epilepsy, there was
medicine) has existed in India from millennia with the
significant down regulation of NMDA R1 gene expression and
objective to treat poor health with economical medicines
glutamate receptor binding without any change in its affinity.
obtained from herbs.
B.monnieri treatment of epileptic rats significantly reversed the
expression of NMDA R1 and glutamate receptor binding
Likewise, different regions across the globe inherit their
alterations to near-control levels. Also, in the epileptic rats, it
traditional system of medicine wherein, in today’s globalized
was observed a significant increase in the activity of glutamate
era these traditional systems should not be restricted to their
dehydrogenase, which neared the control level after B.
native origins but rather be made accessible and used
monnieri treatment107.
throughout the human population. With this regards herbal
anticonvulsants that are successfully exploited are reviewed as
Bryophyllum Pinnatum:
under7.
B. pinnatum aqueous extract might produce its central nervous
system depressant action as consequence of its GABAergic and
On the other hand, herbal medicines are widely used across the
less importantly, glycinergic transmission, since picrotoxin is a
globe due to their wide applicability and therapeutic efficacy
selective GABAA receptor antagonist while strychnine
coupled with least side effects, which in turn has accelerated
antagonizes the inhibitory spinal cord and brainstem reflexes of
the scientific research regarding the antiepileptic activity.
glycine109.
Natural products have contributed significantly in the
discovery of modern drugs and can be an alternative source for
Cissus quadrangularis:
the discovery of AEDs with novel structures and better safety
The inhibition by the extract of C. quadrangularis of STR-
and efficacy profiles. Thus, it is necessary to investigate for an
induced seizures suggests the presence of anticonvulsant
anti epileptic agent that is highly efficacious as well as safe in
1 properties and the involvement of glycine receptors. The
items of drug related toxicity .
sedative properties of C. quadrangularis could be related to the
presence of some components in the extract activating the
O benzodiazepine and/or GABA recaptors in the GABA receptor
complex21.
NH2
HO OH N O Cotyledon orbiculata:
Both aqueous and methanol extracts of Cotyledon orbiculata
have anticonvulsant property and may probably be affecting
both gabaergic and glutaminergic mechanisms to exert its
Cannabidiol Levetiracetam anticonvulsant effect 25.

Cyperus articulates:
Cyperus articulatus showed dose dependent reduction in
O
N spontaneous epileptic form discharge and NMDA induced
depolarization in rat cortical wedge preparation at
Nh2 concentration at which L-amino-3-hydroxy-5methyl-isoxazole-
O 4- propionic acid (AMPA)induced depolarization are not
affected. This indicates that the extract may contain
Brivaracetam components acting as AMPA antagonist responsible for the
possible antiepileptic action27.

An alternative to therapy for epilepsy could be from natural

sources.These medicines may prove superior to synthetic

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 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

Table: 1
S. No Classification Drugs Side effect
1- Hydantion Phenytoin Nausea, skin rashes blood dyscarasias, hyperglycemia cardiac arrhythmias
2- Barbiturate Phenobarbital Dizziness, lethargy, hypotension, aponea, megaloblastic anemia, Liver damage
3- Iminostilbene Carbamazepine Dizziness, ataxia, drowsiness, hallucinations, dermatologic sweating, genitourinary
albuminaria, hypotension, liver dysfunction.
Eslicarbazepine Nausea, Dizziness and headache
4- Oxazolidinedione Trimethadone Drowsiness, G.I.distress, vertigo, diplopia, epistaxis, alopecia, nephrosis, foetal
malformation .
5- Deoxybarbiturate Primidone Lethargy, ataxia, vertigo, irritability, severe skin rashes, lymphadenopathy,
impotence, visual disturbances, lupus like reactions
6- Succinimide Ethosuximide G.I. distress, euphoria, confusion, myopia, urticaria, vaginal bleeding and

7- Aliphatic carboxylic Sodium Nausea, vomiting, indigestion, sedation, abdominal cramps, fetal hepatic failure,
Acid Valproate alopecia, irregular menses, acute pancreases, blood dyscarasias
8- Phenyltriazine Lamotrigine Dizziness, ataxia, blurred vision, vomiting, skin rashes, Stevens Johnson syndrome,
disseminated intravascular coagulation
9- Aromatic allylc alcohol Stiripentol Loss of appetite, drowsiness,cognitive impairment, ataxia, diplopia, nausea,
abdominal pain and occasionally asyptomatic neutropenia.
10 - Carbamoyl ethanol Carisbamate Dizziness, nausea, somnolence and headache.
11 - Triazole Rufinamide Vomiting, somnolence,pyrexia and diarrhoea.
12 - - Lacosamide Dizziness, nausea, somnolence, headache, Vomiting, blurred vision, diplopia and
tremor.
13 - - Retigabine Sedation, dizziness, cognitive impairment, vertigo and diplopia
14 - - Brivaracetam Mostly CNS-related

Table: 2 Common drug-drug interactions

S . No . Antiepileptic drug Other drugs Interactions
1- Phenytoin Antacids Reduced serum phenytoin levels and thus loss of seizure control.
Chlorpheniramine Phenytoin intoxication
2- Barbiturates Caffeine Reduces or abolishes the hypnotic effect of pentobarbitone
Cimetidine /Ranitidine Pentobarbitone reduces the absorption of cimitidine while cimitide
Codeine increases metabolism of
Felbamate pentobarbitone
Miconazole Increases serum level of pentobarbitone.
Rifampicin Increases serum level of pentobarbitone.
Sodium valproate Reduce in the activity of rifampicin by increase in the clearance.
Increase in phenobarbitone level leading to excessive sedation.
Decrease in serum phenobarbitone level
3- Carbamazepine Allopurinol Reduction in absorption of carbamazepine.
Cholestyaramine/ Transient increase in serum carbamazepine. Leads to hyponatraemia.
Colestipol Marked increase in serum carbamazepine levels leading to toxicity.
Cemitidine / Ranitidine Marked increase in serum carbamazepine levels leading to toxicity.
Diuretics Carbamazepine levels are reduced leading to its poor seizure control
Isoniazid
Metronidazole
Primidone
4- Rufinamide Oral hormonal May increase the clearance of Oral hormonal contraceptives as a result of
contraceptives a weak induction of CYP3A4.
5- Carisbamate Oral contraceptives Reduction in Plasma concentration of Carisbamate by 20-30%
6- Brivaracetam Oral contraceptives Slight reduction in absorption

Echium amoenum: part to monoterpenes and terpenoid compounds present in the

It is believed that plants of Boraginaceae family are rich of root50.
fatty acids, especially gamma linoleic acid and flavonoids.
There are some evidences about anticonvulsat effect of this Hypoxis hemerocallidea:
fatty acid and some flavonoid compound.the antiseizure effect Hypoxis hemerocallidea aqueous extract produces its
of E.amoenum Fisch and C.A. Mey (F.M.) may be related in antiseizure effect by enhancing GABAergic neurotransmission
part to linoleic acid and/or flavonoid compounds present in the and/or action in the brain.56
extrat43.

Ferula gummosa: Harpagophytum procumbens:

Modulation of glutamatergic and GABAergic transmission is H.procumbens secondary root aqueous extract produces its
some mechanisms indicated for anticonvulsant action of the anticonvulsant activity by enhancing GABAergic
monoterpenes like linalool and eugenal.therefore,it seems that neurotransmission and/or facilitating GABAergic action in the
the antiseizure profile of F.gummosa root may be related in brain 61.

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 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

Mimosa pudica:
Mimosa pudica used in generalized clonic seizures in man
HO (PTZ model) through GABAnergic neurotransmission. The
inhibition of strychnine induced seizures highlights its
HO indication through glycine receptors. Overall the study revealed
anticonvulsant effect of the drug through modulation of
OH O multiple neurotransmission72.

Baicalein Nardostachys jatamansi:

Nardostachys jatamansi root extract significantally increases
Wogonin
seizure threshold against maximal electroshock seizure (MES)
model as indicated by a decrease in the extension/flexion (E/F)
ratio77.

OH
HO
O OH
OH

OH OH
O O
9
Tetrahydrocannabiol HO O
OH
Harpephyllum caffrum: HO OO
H.caffrum stem-bark aqueous extract might have inhibited OH
and/or attenuated PTZ-and PCT-induced seizures of the mice HOO
OH
used by enhancing, or in some way interfering O O
with,GABAergic neurotransmission and/or action in the HO OH
brain57. OH
HO
Glycyrrhiza glabra:
Anticonvulsant effects of the G. glabra extract could be related OH
HO
to the inhibitory effects of glycyrrhizic acid on gap junction OH
channels.also,there is some evidence that glycyrrhetininic acid
derivatives exert a variety of effects such as altering the activity pentagalloylglucose
of ion transport processes including ion channels and inhibition
Na+-K+-ATPase. Glycyrrhiza extract displays biochemical (C2H5)2NOC CH3
properties, all of which are possible contributors to its N
anticonvulsant effects54.

Gossypin:
Gossypin a bio-flavonoid exhibits anticonvulsant activity and
the probable mode of action may be due to GABAaminergic
mediation, glycine inhibitory mechanism and inhibit the
electrical kindling effect1.
Leonotis leonurus:
The extract of L. leonurus has anticonvulsant activity and may
probably be acting through non-specific mechanisms, since it
affects both gabaergic and glutaminergic systems65.
Lavandula stoechas:
Lavandula stoechas caused a dose dependent (0.1–1.0mg/ml)
relaxation of spontaneous contraction and inhibited K+ induced
contractions thereby, suggesting calcium channel blockade.
Further, pretreatment of the jejunum preparation with L.
Stoechas produced a dose dependent shift of the Ca++ dose
response curve to the right similar to the effect of standard
calcium channel blocking activity 68.
673
N
H
Lysergic acid diethylamide (LSD)
Persea Americana:
Persea americana leaf aqueous extract (PAE) produces its
anticonvulsant effect by enhancing GABAergic
neurotransmission and/or action in the brain82.
Pyrenacanthia staundtii:
Strychnine has been shown to induce convulsion by
modulation of action of glycine on inhibitory neurotransmitter.
However, the aqueous leaf extract of Pyrenacanthia staundtii
blocked the convulsion induced by strychnine indicating the
involvement of glycinergic transmission. Picrotoxin is reported
as GABA receptors antagonist inducing convulsion, but the
extract failed to block the convulsion induced by this agent.
This indicates that the extract is not facilitating the GABA-
ergic transmission 83.
 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

Table 3: Anticonvulsant properties of plant-products-

S.NO PLANT NAME FAMILY PART USED SOLVENT METHOD REF.
1- Acosmium subelegans Leguminaceae, Stem Ethanol PTZ,MES 8
Barks
2- Annona diversifolia Saff. and Annonaceae - - penicillin 9
palmitone
3- Artemisia dracunculus Asteraceae Aerial parts - PTZ,MES 10
(Compositae) -
4- Artemisia verlotorum - Hydroalcoholic PTZ,MES 11
5- Aloe vera Liliaceae - Ethanolic PTZ,MES 12
extracts
6- Albizzia lebbeck Mimosaceae Leaves Ethanolic extract PTZ, electrical kindling 13,14
and
MES
7- Ambrosia paniculata - Leaves - Isoniazid, PCT, and 15
penicillin
8- Acorus tatarinowii Schott Araceae. Rhizomes Decoction and PTZ,MES and 16
volatile oil prolonged PTZ kindling
extracted models
9- Benincasa hispida Cucurbitaceae. Fruit methanolic PTZ, STR and PCT and 17
MES
10- Butea Monosperma Fabaceae Flowers Petroleum ether MES, PTZ, electrical 11
extract kindling and combination
of lithium sulphate with
pilocarpine nitrate
11- Cassia sophera Caesalpiniaceae Seed Ethanol PTZ,MES 18
12- Crocus sativus Iridaceae Stigmas Aqueous PTZ,MES 19 and
andethanol 20
13 Cissus quadrangularis Vitaceae Stems Aqueous PTZ,MES, NMDA, 21
isonicotinic hydrazid acid
Cissus sicyoides Vitaceae Leaves Hydro-alcoholic and STR 22
extract
PTZ
14 Carissa edulis Apocynaceae Root bark - MES,PTZ 23 and
24
15- Cotyledon orbiculata Crassulaceae Leaf Aqueous and PTZ,PCT, 25
methanol BCL and NMDA
16- Cissampelos mucronata Menispermaceae Root extract ethanolic PTZ,MES 26

17- Cyperus articulates Cyperaceae Rhizomes Methanolic PTZ, MES, STR and PCT 27
,aqueous extract,
18- Carissa edulis Apocynaceae Root bark - PTZ,MES 28

19- Casimiroa edulis Rutaceae Seeds, Aqueous, PTZ,MES 29,30

Leaf Methanol and rotarod
20- Cestrum nocturnum Lin Solanaceae Leaves Decoction isoniazid and PCT, 31
maximal electroshock
seizures, penicillin
21- Calotropis procera Asclepiadaceae Root Chloroform, MES,PTZ, lithium- 32
aqueous extract pilocarpine and electrical
kindling seizures
PTZ
Alcoholic
Asclepiadaceae extract -
Calotropis gigantean Roots 33
22- Calliandra portoricensis - Root and aqueous extracts PTZ and electroshock- 34
stem extracts induced convulsions
23- Centranthus longiflorus - - Aqueous extract Caffeine 35
24- Citrus aurantium Rutaceae Peel and Hydroethanolic PTZ,MES 36
leaves
25- Cynodon dactylon Graminae Aerial parts Ethanol extract PTZ 37
26 Cymbopogon winterianus Poaceae Leaves - PTZ- and PIC 38
27- Delphinium denudatum Ranunculaceae Roots Ethanolic extract MES, PTZ, BCL,PCT 39,40
and aqueous and STR
fraction
28- Desmodium adscendens Papillionaceae Leaves Ethanolic extract PTZ 41
29- Diospyros mespiliformis Ebenaceae. Stem bark Aqueous extract PTZ, rota-rod 42
30- Echium Amoenam Boraginaceae Flower Methenol PCT 43
31- Erythrina indica Papilionaceae Leaves Ethanol, PTZ,MES 44
Chloroform and

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 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

Ethyl acetate
extracts
Hydroalcoholic
extracts
Erythrina velutina and Erythrina Fabaceae Stem bark PTZ STR, 45
mulungu.
32- Eugenia caryophyllata Myrtaceae - - PTZ,MES 46
33- Egletes viscose - Flower Essential oil PTZ 47
34- Ficus Sycomoros Moraceae Stem, Ethenol PTZ, STR 4,48
Moraceae Leaves - PTZ
F.religiosa
-
35- Ficus platyphylla Stem bark Methanol extract PTZ,MES and STR 49
36- Ferula Gummosa Apiaceae Root,seed Acetone PTZ,MES and Rotarod 50,51
37- Gossypin Malvaceae - - PTZ,MES,and STR 1
38- Goodyera schlechtendaliana - Whole plants - PCT 52
39- Ginseng Araliaceae Whole root PTZ, kainic 53
leaves/stems Acid and,pilocarpine-
extract, and a induced seizures
partially
purified
extract
40- Glycyrrhiza glabra Leguminosae Root and Aqueous,Ethano PTZ 54,55
Rhizome l
41- Hypoxi hemerocallidea Fisch. and Hypoxidaceae Corm Aqueous PTZ,PCT,BCL 56
C. A. Mey.
42- Harpephyllum caffrum Anacardiaceae Stem Aqueous extract PTZ, PCT 57
43- Heracleum crenatifolium Umbelliferae Fruits Acetone extract MES 58
Heracleum persicum Seed PTZ,MES 59
44- Hibiscus rosasinesis Malvaceae Flowers Ethanolic PTZ,MES 11
Extract
45- Hypericum perforatum Hypericaceae Aerial part Aqueous and PTZ,MES 60
ethanol extract
46- Harpagophytum procumbens DC Pedaliaceae Root Aqueous extract PTZ, PCT and BCL 61
47- Ipomoea stans Root Ethyl acetate PTZ 62
extract
48- Kalanchoe crenata (Andrews) Crassulaceae Leaves Methylene PTZ, strychnine sulphate 63
Haworth chloride/methan (STN) And
ol thiosemicarbazide (TSC)
49- Lecaniodiscus cupanioides - Root Aqueous extract STR ,PCT 64
50- Leonotis leonurus Lamiaceae Leaves Aqueous PTZ, PCT,BCL 65
and NMDA
51- laurus nobilis Lauraceae Leaf - MES and PTZ 66
52- Lychnophora rupestris and L. Vernonieae, Stem Polar extracts PTZ 67
staavioides Asteraceae and methanolic
fractions
53- Lavandula stoechas Labiatae Flowers Aqueous PTZ 68
methanolic
extract
54- Maprounea Africana Euphorbiaceae Leaves Ethanolic extract PTZ, 69
55- Mitragyna africanus Rubiaceae Stem bark Methanol extract STR 70
56- Mitragyna africanus Rubiaceae Stem bark Methanol extract STR 71
57- Mimosa pudica Mimosaceae Leaf Decoction PTZ,PCT , STR 72
and,NMDA
58- Moringa oleifera Moringaceae Roots Methanolic PTZ, STR 73
extract
59- Myristica fragrans Myristicaceae Seeds Petroleum PTZ,MES,PCT 74
Ether lithium pilocarpine
60- Magnolia dealbata Magnoliaceae Leaves Ethanol extract PTZ 75
Ethyl ether (EE)
Magnolia grandiflora Seeds and MES 76
hydroalcoholic
extract
61- Nardostachys jatamansi Valerianaceae Roots Ethanol PTZ,MES 77
62- Nigella sativa Ranunculaceae Seeds - PTZ,MES 78
63- Nepeta sibthorpii Labiatae - Methanol PTZ 79
(lamiaceae)
64- Nylandtia spinosa L. Dumont Polygalaceae Leaf Aqueous and PTZ, bicuculline, PCT, 80
methanol and NMDLA.
65- Ocimum sanctum Labiatae; Stem, leaf Ethanol and MES 81

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 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

Lamiaceae. and stem chloroform

extract
66- Persea Americana Lauraceae Leaf Aqueous extract PTZ,PCT, BCL 82
67- Pyrenacanthia staundtii Icacinacae Leaf Aqueous PCT, STR 83
68- Passiflora incarnate Passifloraceae Aerial parts Hydro- alcoholic PTZ 84
(leaves, extract
flower and
fruit)
69- Pimpinella anisum Umbelliferae Fruits Aqueous PTZ,MES 85
70- Piper guineense Piperaceae. - Water extract NMDLA, PTZ,MES 86
71- Petiveria alliacea Phytolaccaceae Root Acetate, Rotarod, PTZ 87
hexane,hydroalc
oholic and
precipitated
hydroalcoholic
72- Rosa damascena Rasaceae Petel PTZ 88
73- Rubus brasiliensis, Rosaceae Leaf Ethanol - 89
74- Rhus chirindensis Anacardiaceae Stem-bark Aqueous extract PTZ, PCT and BCL 90
75- Ruta chalepensis Rutaceae. Aerial parts Ethanol extract PTZ 91
76- Sclerocarya birrea Anacardiaceae Stem bark Aqueous extract PTZ,PCT,BCL 92,93
77- Scutellariae radix Labiatae Root Water extract MES, PTZ 94
(lamiaceae)
78- Sapindus trifoliatus Sapindaceae Fruits Aqueous PTZ,MES and rotarod 95
79- Schumanniophyton magnificum - Roots Ethanolic PCT and STR 96
80- Sutherlandia frutescens Fabaceae Shoot Aqueous extract PTZ, PCT and BCL 97
81- Sesbania grandiflora Papilionaceae; Leaves - PTZ and STR, lithium- 98
Fabaceae. pilocarpine
82- Sanseviera liberica Gerome and Agavaceae Root Aqueous strychnine, picrotoxin, 99
Labroy bicuculline and
pentylenetetrazole
83- Spondias mombin Anacardiaceae. Leaves Aqueous, PTZ, picrotoxin 100
methanol and
ethanol
84- Taxus wallichiana Taxaceae Leaf Methanol PTZ 101
85- Tetrapleura tetraptera Fabaceae Fruit Aqueous extract PTZ, PCT and BCL 103
86- Vitex-negundo Verbenaceae Leaf Ethanol PTZ,MES 104
Vitex negundo Verbenaceae Leaf Petroleum ether STR and leptazole 105
Hydroalcohol rotarod
87- Valeriana edulis - Roots 106
88- Withania somnifera Solanaceae Root - PTZ 107
Pentylenetetrazole (PTZ), Picrotoxin (PCT) and Bicuculline (BCL), N-methyl-DL-aspartic acid( NMDA) and Strychnine
(STR)

Rubus brasiliensis: produced by wogonin were mediated by the GABAergic

Rubus brasiliensis leaf ethanol extract was found to contain a
benzodiazepine like principle and hence indicated possible
involvement of GABA–A receptors. This involvement is
further supported by reversal of anxiolysis in rodents induced
by lumozenil, a specific GABA –A – benzodiazepine receptor
antagonist89.
neuron108.
Sutherlandia frutescens:
S. frurescens shoot aqueous extract produces its antiseizure
effect directly by acting like GABA, or indirectly by enhancing
GABAergic neurotransmission and/or action in the brain.97

Sclerocarya birrea: Natural lead compounds:

Sclerocarya birrea produces its anticonvulsant effect by The use of medicinal plants for the treatment of epilepsy and
enhancing GABAergic neurotransmission and/or action in the convulsive disorders dates back to prehistoric times. Several
brain92. plants that were reputed to possess antiepileptic properties in
different folklore cultures have been found to contain active
Scutellaria baicalensis: ingredients when tested with modern bioassays for detecting
Wogonin is a natural product isolated from S. baicalensis, anticonvulsive activities. This provides justification for their
which possesses central nervous system effects such as use in many different indigenous medicinal systems. The
anxiolytic and neuroprotective activities. Wogonin injected activity of many other plants however remains to be
intraperitoneally significantly blocked convulsion induced by scientifically established. Ethnopharmacological research on
pentylenetetrazole and electroshock but not convulsion induced natural products can contribute to the discovery of new active
by strychnine. Wogonin also significantly reduced the compounds with novel structures which may serve as leads to
electrogenic response score, but flumazenil treatment reversed development of new antiepileptic drugs. An example is the
this decrease to the level of the control group. The wogonin isolation of the active alkaloid piperine from Piper nigrum L.
increased Cl-influx whereas Flumazenil and bicuculline inhibit which is one of the component herbs of an ancient Chinese
it. These results indicate that the anticonvulsive effects medicine used for the treatment of epilepsy. Its structural
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 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

modifications resulted in the synthesis of seven derivatives activity. In FeCl3-induced epilepsy model it significantly
including antiepilepserine which was found to be more potent decreased the level of free radicals at the injection site in the rat
than the parent compound with fewer side effects and it has brain.
been used as an antiepileptic drug.
A number of highly addictive and toxic compounds have been
The aqueous extract as well as its albiflorin and isolated from these plants; including LSD, 8 and 9
8
pentagalloylglucose isolated from Paeonia albiflora (peony), a tetrahydrocannabinols, cannabidiol and cocaine. and 9
constituent of TJ 960, have strong inhibitory effect on PTZ tetrahydrocannabinols have anticonvulsant activity in various
induced EEG activity and Ca++ and K+ ion concentration experimental models of epilepsy including kindling.
changes related to seizures. The extract has also shown to
inhibit PTZ induced intracellular Ca++ release and inward Ca++
current. Methysticin, a kava pyrone isolated from the rhizomes
of Piper methysticum(which is a shrub indigenous to south
Pacific islands) and its dihydro derivative have neuroprotective O OH
effects in addition to anticonvulsant properties. Methysticin
also inhibits seizure-like events in three different models of
epileptiform activities in hippocampal and entorhinal cortex
slices.
8
Linalool a monoterpene isolated from several species of
Tetrahydrocannabiol
aromatic plants including Aeolanthus suaveolens G.Dom.,
which is used for treatment of convulsions in Brazilian
Amazon, has inhibitory effect on glutamate binding in rat
cerebral cortex preparations. Baicalein isolated from TJ-960
exhibited strong in vitro radical scavenging and antioxidative
Rufinamide
Eslicarbazepine
Exitatory Lacosamide
Inhibitory synapse
synapse

Brivaracetam NA+

GABA GABA-B
Ca++
VGCC
SV2A
NA+
CL
Stiripentol
Ca++
Retigabine AMPA
GABA-A

NMDA
K

VGPC mGluR

NA+
Intracellular signalling pathways regulating Ca++
VGSC excitability in the poststynaptic neuron
VGC
C

Fig. proposed mechanism of action for new antiepileptic drugs(AEDs)that have recently been approved or
are in late-stage developement.Proposed molecular targets for these new AEDs are shown, with dark
arrows pointing to the GABA-A receptor, GABA reuptake, the synaptic vesicle protien
2A(SV2A),intracellular signalling protiens, and voltage-gated sodium channels(VGSC )and voltage gated
potassium channels(VGPC). The mechanism of action of carisbamate is still not known.AMPA=alpha
amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid; mGluR=metabotropic glutamate receptor;
VGCC=voltage gated calcium channel.

677
 Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009

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