ANTICONVULSANT DRUGS.pptx-classification mechanism structure synthesis

ANTICONVULSANT DRUGS

1. ANTICONVULSANT DRUGS Presented by, Chinnu Suresh 1 st semester Mpharm Pharmaceutical Chemistry

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) Generalised epilepsy : It affect both sides of brain Absence seizures Atonic seizures Myoclonic seizures Infantile seizure 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.

6. Classification ( i )Barbiturates: eg. Phenobarbitone, Mephobarbitone . (ii)Hydantoins: eg. Phenytoin, Mephenytoin, Ethotoin . (iii) Oxazolidinediones : eg. Trimethadione, Paramethadione. (iv) Succinamides : eg.Phensuximide , Methsuximide , Ethosuximide (v) Iminostilbenes : eg. Carbamazepine, Oxcarbazine . (vi)Benzodiazepines: eg. Clonazepam, Diazepam, Chlorazepate . (vii)Newer antiepileptic: eg. Valproic acid, Zonisamide , Gabapentin, Tiagabine, Felbamate, Vigabatrin, Lamotrigine. (viii)Miscellaneous: eg. Primidone, Phenacemide.

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

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

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

12. Paramethadione( paradione ) Uses :It is used in the treatment of petitmal epilepsy

13. Succinamide Name R R₂ R₃ Phensuximide C₆H₅ H CH₃ Methsuximide C₆H₅ CH₃ CH₃ ethosuximide C₂H₅ CH₃ H

14. Phensuximide Synthesis

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.

16. Iminostilbenes A) Carbamazepine Carbamazepine contain a dibenzazepine ring system with a carbonyl moiety hooked on the nitrogen atom. Uses: Used to control grand mal and focal seizures.

17. Benzodiazepines Clonazepam Uses: Effective in all type of epilepsy like grand mal, myoclonic and status epilepsy.

18. Newer Antiepileptics Valproic acid 2-propyl pentanoic acid Synthesis

19. Miscellaneous agents Primidone Synthesis Uses: It is a potent anticonvulsant

20. REFERENCE Textbook of Medicinal chemistry by k.iiango and p valentina . Page nbr 207

21. THANK YOU