Inhibitor of GABA

Veratridine appears to act at a different part of pore channel from DDT or pyrethroids Act as agonists causing desensitization of receptor Inhibitor of GABA receptors... 

Disorders of GABA Vitamin B6-dependent seizures Often an absence of succinic semialdehyde dehydrogenase Hypotonia, ataxia, mental retardation in older child. Increased urine 4-OH-butyric acid. Pyridoxine (B6-dependent disorder) Inhibitors of GABA transaminase... 

Tiagabine is a specific inhibitor of GABA reuptake into glial cells and other neurons. 

Wood, J. D., Schousboe, A., and Krogsgaard-Larsen, P. (1980) In vivo changes in the GABA content of nerve endings (synaptosomes) induced by inhibitors of GABA uptake. Neuropharmacology 19,1149-1152. 

Of the many drugs that have been developed which modulate GABA function, the inhibitors of GABA transaminase have been shown to be effective anticonvulsants. These are derivatives of valproic acid that not only inhibit the metabolism of GABA but may also act as antagonists of the GABA autoreceptor and thereby enhance the release of the neurotransmitter. GABA-uptake inhibitors have also been developed (for example, derivatives... 

They are different from vigabatrin (4) in that they are not inhibitors of GABA transaminase, and, in contrast to tiagabine (5), these molecules do not directly inhibit GABA reuptake (Bryans and Wustrow, 1999 Taylor, 1994). 

Vigabatrin is a new antiepileptic for use in epilepsy unresponsive to other therapy. It is an irreversible inhibitor of GABA-transaminase, the enzyme responsible for inactivation of the neurotransmitter GABA and it has shown efficacy against partial and secondarily generalized seizures. The principal unwanted effects are psychiatric disorders, including depression and psychosis, in a small number of patients. 

Figure 7.50 Conformationally restricted fluorinated inhibitors of GABA-AT...

The answer is c. (Hardman, p 481. Katzung, pp 404-405.) Vigabatrin is useful in partial seizures. It is an irreversible inhibitor of GABA aminotransferase, an enzyme responsible for the termination of GABA action. This results in accumulation of GABA at synaptic sites, thereby enhancing its effect. 

It is an inhibitor of GABA transaminase which degrades GABA. It suppresses maximal electroshock and kindled seizures and is used in partial seizure with or without generalization. 

Further fluorinated synthons 20 (equation 17)92 and 21 lead to Reformatsky intermediates which are synthetic equivalents of a formal 4,4-difluoroacetoacetate dianion and of a carbalkoxy trifluoromethyl carbene, respectively. The latter has been exploited in a synthesis of E-22 and Z-22, both inhibitors of GABA aminotransferase (equation 18)93. 

Tiagabine is a derivative of nipecotic acid and was "rationally designed" as an inhibitor of GABA uptake (as opposed to discovery through random... 

Based on this premise, y-acetylenic GABA (IV) waB synthesized (11) and found to be an irreversible inhibitor of GABA-T, in vitro and in vivo (12). Thus, when GABA-T, partially purified from pig brain, is incubated for varying time periods with y-acetylenic GABA, a time-dependent inactivation process is observed which follows pseudo first-order kinetics. Enzyme half lives range from 28 minutes to 9 minutes with concentrations of inhibitor between 0.029 mM and 0.29 mM. Time dependent inactivation is... 

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