Review of Pharmacology - 9E (2015)

Review of Pharmacology
(b) Increase in Inhibitory Neurotransmission:
GABA is a major inhibitory neurotransmitter in the brain. Barbiturates (phenobarbitone,
primidone) and benzodiazepines (diazepam, clonazepam, clobazam) activate GABAA
receptors by binding to GABA-BZD-Cl – channel complex. Ganaxolone (a neurosteroid)
also acts by activating this channel but the binding site is different. Drugs can also
act by increasing the release (Gabapentin), decreasing the metabolism (Vigabatrin) or
inhibiting the reuptake in neurons (Tiagabine).
(c) Decrease in Excitatory Neurotransmission:
Glutamate and aspartate are major excitatory amino acids in the brain. Glutamate
can act by stimulating metabotropic (GPCRs) or ionotropic receptors (kainate,
NMDA and AMPA). Felbamate acts by inhibiting NMDA receptors. Topiramate act
by inhibiting kainate receptors.
(d) Inhibition of Ca 2+ Channels:
T-type Ca 2+ channels are important in absence seizures. Drugs inhibiting these
channels (ethosuximide, valproate, lamotrigine) are useful in petit mal epilepsy.
Mechanism of action of anti epileptic drugs
Central Nervous System
DRUG ↑ Gaba activity ↓ Glutamate
Activity
1. Phenytoin
2. Carbamazepine
Prolong
inactivated
Na +
channels
3. Valproate (a)
4. Lamotrigine (b)
5. Ethosuximide
6. Gabapentin (c)
Block
T-ca 2+
Channels
Other
7. Topiramate (d) (e) Activates
K + Channel
8. Tiagabine (f)
9. Phenobarbitone (g)
10. Primidone (g)
11. Benzodiazepines (g)
12. Felbamate (h)
13. Levetiracetam Block SV 2
A
14. Zonisamide
15. Lacosamide CRMP-2
inhibitor
16. Rufinamide
17. Retigabine
(Ezogabine)
K +
channel
opener
a - Increase GABA by activating Glutamic acid decarboxylase and inhibiting GABA transaminase
b - Inhibits release of glutamate
c - Inhibits release of GABA
d - Increases postsynaptic GABA activity
e - Blocks AMPA receptors of glutamate
f - Inhibits reuptake of GABA by inhibiting GAT-1
g - Act on GABA-BZD-Cl – channel complex
h - Blocks NMDA receptors of glutamate
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