DRUGS ACTING ON CNS-ANTI CONVULSANT DRUGS

ANTI CONVULSANT DRUGS (OR) ANTI EPILEPTIC DRUGS

Epilepsy is a collective term for a group of chronic CNS disorders having in common, sudden and transitory seizers of loss or disturbance of consciousness with characteristic body movements (convulsions) and some times with autonomic hyperactivity.
The principal types of epilepsy are
1. Grandmal epilepsy:
It is normally characterized by complete loss of consciousness followed by transient muscular rigidity and clonic convulsions in all voluntary muscles.
2.Petitmal epilepsy :
It is usually momentary loss of consciousness. There is free of convulsions and occasionally blinking movements of eyelids and jerking movements of the head and arms.
3.Psychomotor epilepsy :
It is characterized by attacks with out convulsions lasting from 2-3 mts. It display mental apathy and sudden irrational and destructive attitude.
4.Myoclonic seizers :
It is characterized by jerky muscular movements of head, limbs or body as such. The duration of attack remains near about one second and reappears at about 5 secs intervals for 1 min. It is rapid rhythmic movement.
Anti Convulsants:
Anti Convulsant drugs are also termed as antiepileptic drugs are drugs which selectively depress the CNS and prevent or control the epileptic seizers.
The drugs are adequate and impressive control and management of CNS disorders essentially characterized by recurrent transient attacks of disturbed brain function which ultimately give rise to motor(convulsive), sensory(seizures) and psychic sequence of events.

CLASSIFICATION

1. Barbiturates – Phenobarbital, Mepho barbital, Metharbital


2. Hydantoins – Phenytoin, Mephenytoin, Ethotoin


3. Oxazolidine dione - Trimethadione, Paramethadione


4. Succinimides – Phen suximide, Methsuximide, Ethosuximide


5. Urea derivatives – Phenacemide, Carbamezepine


6. Benzodiazepines – Clonazepam, Diazepam, Chlorazepate


7. Miscellaneous – Primidone, Valproic acid, Gabapectin, Felbamate.
   

1. BARBITURATES

2. HYDANTOINS

Synthesis of phenytoin

3.OXAZOLIDINEDIONES

Synthesis of Trimethadione

4. SUCCINIMIDES

Synthesis of Ethosuximide

5.UREA DERIVATIVES

i. Phenacemide

2.Carbamazepine

6. BENZODIAZEPINES

Clonazepam

7. MISCELLANEOUS

i.Pyrimidone

ii. Valproic acid

Structure Activity Relationship

For Barbiturates

1. Phenyl or other aromatic substituents at 5th position is essential for good activity.


2. 5,5 diphenyl derivative has less active than phanobarbitone.


3. N-substitutions also increases the antiepileptic activity.


4. 5,5-dibenzyl barbiturates causes convulsions.

For Hydantoins

1. Phenyl or other aromatic substituents at 5th position is essential for good activity.


2. Alkyl substitution at 5th position may contribute to sedation.


3. Some Thio hydantoins, Dithio hydantoins and 1,3-disubstituted hydantoins exhibit activity against chemically induced convulsions and ineffective against electroshock induced convulsions.

For Oxazolidine diones

1. The nature of substituents at 5th position is essential for good activity.


2. The lower substituents tend towards anti-petitmal epileptic activity and aryl towards anti-grandmal epileptic activity.


3. N-alkyl substituents does not affect the activity, because the N-dealkylated metabolites are active anticonvulsant agents.


4. Alkylation of imido nitrogen is more active, because it increase partition coefficient and prevent the dissociation of imido nitrogen and more distribution to CNS.

For Succinimides

1. Meth suximide and phen suximide have phenyl substituents at 3rd position are active ineffective against electroshock induced convulsions.


2. N-methylation decreases the activity against electroshock induced convulsions and more activity against chemically induced convulsions.


3. Alpha-methyl alkoxy phenyl succinimides and alkoxy benzyl succinimides were active anti convulsants.

For Benzodiazepines

1. The electron withdrawing groups at 7th position increases antiepileptic activity and electron donating groups at 7th position increases antiepileptic activity.


2. A phenyl group at 5th position is necessary for good activity. But the halogen substituents in phenyl group in ortho position increase the activity.


3. The electron withdrawing groups at ortho or diortho positions at 5-Phenyl group increases antiepileptic activity while any substituent on meta or para position of 5-Phenyl group decreases antiepileptic activity.


4. Methyl substitution at 1st position increases the activity.

Mechanism of action

1. The generation of seizures is due to excessive discharge of neurotransmitter in CNS.The anti convulsant drugs increase the level of serotonin in brain which causes non specific depression of CNS functions and controls the release of neurotransmitters.


2. Gama Amino Butyric Acid(GABA) levels in brain is also important to prevent the speed of seizures. So anti convulsant drugs increase the level of GABA in brain.


3. Anti convulsant activity of barbiturates is attributed to their ability to exert conformational rearrangement of oxidative enzymes essential for brain respiration.


4. Many carbonic an hydrase inhibitors have Anti convulsant activity by decreasing the cerebral respiration due to excess Co2 depress the nerve function.


5. Anti convulsant drugs usually display various combined activities on the neuronal function such as act on ion channels and maintain the neuronal membrane, the resting potential having range of -50 mv to -80 mv between inside (K+) and outside (Na+ & Cl-) of the cell.


6. GABA binds to GABA A and GABA B receptors. The oscillation rhythms in epilepsy caused by GABA A receptors. Therefore the drugs potenciate GABA mediated inhibitors or to affect the GABA concentration in brain.