2. It is also known as Anti-epileptic OR Anti seizure drug
These are those drugs which are used to treat epilepsy
and seizure.
Epilepsy: it is a chronic disorder characterized by
paroxysmal brain dysfunction due to excessive neuronal
discharge and usually associated with some alteration of
consciousness.
Convulsion: Involuntary spasmodic contractions of any
or all voluntary muscles throughout the body, including
skeletal and facial muscles.
3. Types of epilepsy (epileptic seizures)
A. Generalised epilepsy: It affect both sides of brain
• Absence seizures
• Atonic seizures
• Myoclonic seizures
• Infantile seizure
B. Partial seizures:
Simple partial seizures
Complex partial seizures
Simple partial or complex partial seizures secondarily generalized.
4. Mechanism of Action
Some drugs block sodium channel: Epileptic seizure causes Na
ion accumulation within the central neuron, which initiates
enhanced synaptic nerve transmissions following presynaptic
stimulation. These drugs decreases Na intracellular ion by activating
biochemical process that normally extrudes Na ion from neurons.
Prolongation of this inactive state with prolongation of the
refractory period is the principle of mechanism.
Some drugs block calcium channel: A low threshold calcium
current govern oscillatory response in thalamic neuron.
5. Some drugs affect synaptic transmission: Enhances GABA mediated
inhibition.
Some drugs act on excitatory Glutamatergic neurotransmission:
They block glutamatergic receptor
Some drugs act on GABA: They act by decreasing reuptake or
decreasing metabolism of GABA.
7. Barbiturates
Most of the barbiturates are sedatives and hypnotics.
Only few show anticonvulsant activity they are:
phenobarbitone, mephobarbitone, Metharbital
Name R₁ R₂ R₃
Phenobarbitone C₂H₅ C₆H₅ H
Mephobarbitone C₂H₅ C₆H₅ CH₃
Metharbital CH₃ CH₃ CH₃
N
3
4
2
5
N
H
1
6
O
O
O
R
1
R
2
R
3
8. SAR of Barbiturates
Optimum activity is obtained when one of the
substituents at C₅ is phenyl.
The 5,5- diphenyl derivatives have less activity than
phenobarbitone.
Substituents at N₃ some cases cause increased activity
5,5-dibenzyl barbituric acid causes convulsion.
9. Hydantoin
Hydantoin are close relates to barbituric acid, only the
different is the 6-oxo group.
The lack of carbonyl group decreases the acidity
Name R₃ R₂ R₁
Phenytoin C₆H₅ C₆H₅ H
Mephenytoin C₆H₅ C₂H₅ CH₃
Ethotoin C₆H₅ H C₂H₅
N NH
R
1
O
O
R
3
R
2
10. SAR
A phenyl or other aromatic substituents at C5 is
essential for the the activity
Alkyl substituent at position 5 may contribute to
sedation, a property absent in phenytoin
1,3-disubstituted hydantoin which exhibit activity
against chemically induced convulsion
11. Oxazolidinediones
Replacement of the NH group at position one of the hydantoin ring with
oxygen atom yield oxazolidine-2,4- dione system.
Trimethadione(Trioxidone)
Synthesis
+
ethyl-2-hydroxy-2-methylpropanoate 5,5-dimethyl-1,3-oxazolidine-2,4-dione
N
O
CH3
O
O
C
H3
C
H3
N
H2 NH2
O
urea
C2H5ONa
NH
O
O
O
C
H3
C
H3
(CH3)2SO4
NaOH
N
O
CH3
O
O
C
H3
C
H3
3,5,5-trimethyl-1,3-oxazolidine-2,4-dione
OH
C
H3
C
H3 COOC2H5
15. SAR
Methsuximide and phensuximide have phenyl substituents which
make them active against electrically induced convulsion.
N-Methylation decreases activity against electroshock seizures
and impart more activity against chemically induced convulsion.
