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FACULTY OF PHARMACY
PADJADJARAN UNIVERSITY
JATINANGOR
2018
CHAPTER I
INTRODUCTION
Research Background
The term seizure refers to a transient alteration of behavior due to the disordered, synchronous, and
rhythmic firing of populations of brain neurons. The term epilepsy refers to a disorder of brain function
characterized by the periodic and unpredictable occurrence of seizures (Brunton dkk., 2010). Epilepsy
is the most common serious neurological disorder affecting an estimated 50 million people worldwide.
The striking synergism between hypertension and stroke is more epileptogenic than other risk factors.
The involvement of noradrenergic system in modulation of seizure activity is well documented. The
noradrenergic system was demonstrated to participate in the occurrence ofseizure in epileptic EL mice
and to increase epileptiform discharge in rat limbic system via β-adrenergic receptor stimulation (Singh,
2017).
Anticonvulsants (also commonly known as antiepileptic drugs [AEDs]) are a diverse group of
pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being
used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and for the
treatment of neuropathic pain. The goal of an anticonvulsant is to suppress the rapid and excessive firing
of neurons that start a seizure. Failing this, an effective anticonvulsant would prevent the spread of the
seizure within the brain and offer protection against possible excitotoxic effects, which may result in
brain damage (Nirmala, 2015).
To control epileptic seizures, about 60-70% of total epilepsy patients depend on medical
treatment with antiepileptic drugs (Yemadje et al., 2011). The duration of epilepsy treatment is
difficult to determine, in general therapy is given for years so that chronic use of drugs is
associated with central nervous system side effects (Cramer et al., 2010).
Carbamazepine, phenytoin and Gabapentin are some of the anticonvulsant drugs. Carbamazepine is an
iminostilbene derivative that is similar to tricyclic antidepressants and is used in the treatment of clonic,
partial or general tonic seizures. Phenytoin is an anticonvulsant drug that is widely used and effective
against partial and clonic tonic seizures except the absence seizure. Gabapentin is an effective adjunct
therapy for partial seizures, with and without secondary generalization that cannot be controlled with
other antiepileptics.
This study was conducted to study and determine the effects of carbamazepine, phenytoin, and
gabapentin as anticonvulsant drugs in mice tested animals and their ability to resist seizures caused by
administration of theophylline.
Identification of Problems
Based on the background described above, problems that can be identified are:
1. What are the effects of anticonvulsant drugs such as carbamazepine, phenytoin and gabapentin
in mice test animals?
2. How long can anticonvulsant drugs resist seizures (indicating the level of anticonvulsant activity)
caused by induction of theophylline?
3. Which drugs have the highest anticonvulsant activity between carbamazepine, phenytoin and
gabapentin?
Research Purposes
1. Knowing the effects of anticonvulsant drugs such as carbamazepine, phenytoin and gabapentin
in mice test animals.
2. Observe how long anticonvulsant drugs are able to resist seizures (indicating the level of
anticonvulsant activity) caused by the administration of theophylline which functions as an
induction of seizures.
3. Knowing anticonvulsant drugs that have the highest activity between carbamazepine, phenytoin
and gabapentin
usefulness of research
Research Methods
Research will be carried out by the method of induction of seizures using theophylline
CHAPTER III
RESEARCH METHODS
3.1 Tools
The tools used in the study were stirring rods, 250 mL glass beaker, 100 mL glass beaker, mortar,
3.2 Materials
Male mice weighing 25-30 grams 3-4 months old are kept in clean polypropylene cages
with 12 hours of light / dark cycles at 25 ± 2ºC and 65 ± 5% humidity. The cage contains 20 male
0.9% sodium chloride, diazepam (0.28 mg / 20g), Gabapentin capsules 300 mg (0.84
mg / 20g), phenytoin capsules 100 mg (0.4 mg / 20g), carbamazepine tablets 200 mg (1.4 mg /
In this research, there are 5 types of solutions, a negative control solution, positive
control solution, 1 test solution, 2 test solutions, and 3 test solutions. Making negative control
solution is 5% PGA solution by means of 10 gram PGA weighed by analytic scales which have
previously been in tara. Then dissolved with 200 mL of water in a brown bottle and stirred.
Furthermore, the positive control solution, dia. Diazepam was weighed with analytical scales
using spatel and parchment paper mat. Then a little 5% PGA solution is put into a chocolate
bottle, the results of the diazepam scales are put into a chocolate bottle and then homogenized
solution namely theophylline solution was made by means of 10 retaphyl theophylline 300 mg
tablets which were crushed using mortars and stampers until smooth then tablet powder was
weighed with an analytical scale of 3.733 g and dissolved in a beaker with 100 mL 0.9% sodium
chloride solution homogenized by stirring using a stirring rod, then pouring it into a brown
bottle. Furthermore, the test solution 1, crushed 1 carbamazepine 200 mg tablet to the powder
using a mortar and Stemper then weighed 105 mg and dissolved in PGA5% solution as much as
capsule powder and then put in a chocolate bottle which contained a small amount of 5% PGA
solution and homogenized and added 5% PGA solution to a volume of 30 mL, stirring until
homogeneous. Test solution 3, weighed powder capsules of gabapentin 300 mg as much as 67.2
mg then put in a chocolate bottle which contained a small amount of 5% PGA solution and
homogenized and added a 5% PGA solution to a volume of 30 mL, stirring until homogeneous.
Research procedure
This test for anticonvulsant activity requires 20 male mice, divided into 4 groups. Each
group consisted of 5 mice for 5 test groups. Each mice given the drug below, is injected
intraperitoneally (i.p).
i.p of 14 mg / 20 g. Each mouse is placed in an individual plastic cage for observations lasting 30
minutes. Record the time of the first seizure, how long the seizure occurred and the time when