Indications for the use of gamma-aminobutyric acid (GABA)-agonists in convulsant disorders.
From studies using pharmacological models of convulsive disorders and also from the neurochemical analysis of epileptogenic tissue removed during neurosurgical resection (cortectomy), there is strong evidence that at least a subgroup of epileptic disorders may be linked (among other things) to a deficit in GABAergic neurotransmissions. This deficit may be found at the level of GABA synthesis or at the GABA-recognition site; whether these GABA neurons are lost or are dysfunctional is not yet answered. This suggests that GABA-agonists will be of potential use in epilepsy. GABA-agonists (progabide, SL 75102, muscimol, THIP) for the classical GABA-recognition sites as well as other compounds active at sites in the GABA-receptor macromolecular complex (eg, diazepam and phenobarbital) exhibit a wide range of anticonvulsant effects in different animal models and species. However, for some of these compounds (eg, muscimol) secondary central effects occur at the same dose level as the anticonvulsant actions, and for others (eg, THIP) such secondary effects may limit the use to certain types of seizures. This problem may be related to the high affinity of such compounds for the GABA recognition site as compounds with a more moderate affinity (eg, progabide, SL 75102) have a wider margin between anticonvulsant and secondary central effects in rodents. Clinical results using progabide suggests that the GABA hypothesis of convulsive disorders has indeed a rational foundation as a significant percent of refractory or unresponsive epileptic patients with different types of seizures (eg, complex partial or primary generalized) have a significant clinical improvement with this GABA-agonist.
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D004195:Disease Models, Animal; D004828:Epilepsies, Partial / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D009420:Nervous System / Q000032:analysis; D010215:Papio; D012640:Seizures / Q000209:etiology; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000502:physiology* / Q000627:therapeutic use
D000927:Anticonvulsants; C017985:progabide; D005680:gamma-Aminobutyric Acid