Agonist, GABA

Fig. 15. Drug binding sites associated with the GABA receptor—channel complex where (— -) represents the carbon backbone of GABA agonists.

Lhuintre JP, Moore ND, Saligaut C, et ah Ability of calcium bis acetyl homotaurinate, a GABA agonist, to prevent relapse in weaned alcoholics. Lancet 1 1014-1016, 1985... 

Vigabatrin has an unacceptable adverse effect profile, but consistent findings in animal studies suggest that GABA agonists deserve further study. a-AMPA antagonism, or antikindling action, may also be important for some anticonvulsants. 

Lyden PD, Jackson-Friedman C, Shin C, Hassid S. Synergistic combinatorial stroke therapy a quantal bioassay of a gaba agonist and a glutamate antagonist. Exp Neurol 2000 163 477 89. 

Haefliger, W., Revesz, L., Maurer, R., Romer, D., and Buscher, H.-H. (1984) Analgesic GABA agonists. Synthesis and structure-activity studies on analogues and derivatives of muscimol and THIP. Eur. J. Med. Chem. 19,149-156. 

Jones HE, Balster RL. (1998). Muscimol-like discriminative stimulus effects of GABA agonists in rats. Pharmacol Blochem Behav. 59(2) 319-26. 

Degroot A, Parent M. 2001. Infusions of physostigmine into the hippocampus or the entorhinal cortex attenuate avoidance retention deficits produced by intra-septal infusions of the GABA agonist muscimol. Brain Research 920(1-2) 10-18. 

Parent MB, Gold PE. 1997. Intra-septal infusions of glucose potentiate inhibitory avoidance deficits when co-infused with the GABA agonist muscimol. Brain Res 745(1—2) 317-320. 

Pregabaline is primarily an antiepileptic. Although it is an analogue of the neurotransmitter GABA it is not a GABA-agonist. It is mentioned here because it is also approved for use in generalized anxiety states. 

Baclofen is a GABA agonist at GABA B receptors and it has a presynaptic inhibitory function by reducing calcium influx. Its indication is increased extensor tone and clonus. Intrathecal administration may control severe spasticity pain. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis and amyotrophic lateral sclerosis. Its central nervous system effects include drowsiness, somnolence and seizure activity in epileptic patients. 

After a decrease in the importance of steroids in the field of drug research during the last 20 years, a renewal is now being observed. Recently, some fluorinated and fluoroalkylated steroids have been launched or are in advanced phases of clinical development, such as the dutasteride (5a-reductase inhibitor), CCD-3693 (GABA agonist), fulvestrant and antiprogestine (antihormone), and fluasterone (diabetes) (Figure 4.14). Details on the synthesis on these compounds can be found in Chapter 8. 

The cortical, hippocampal, and thalamic GABAergic neurons are crucial for the inhibition of excitatory neurons. Foci of local imbalance, with a subnormal tone of GABAergic inhibition, may spread to distant areas to induce a seizure. GABA agonists such as benzodiazepines or barbiturates can decrease the occurrence of seizures or interrupt ongoing seizure activity (Bazil and Pedley, 1998). 

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