Drug GABA-agonists

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

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. 

GABA Receptors Postsynaptic Drug Effects 4.7.4.1 GABA Agonists... 

The second category consists of only one drug, piperazine, an older agent that apparently acts as a GABA agonist at the neuromuscular junction and causes flaccid paralysis of the nematode. 

Spasticity results from lesions at various sites within the central nervous system and spinal cord. Drugs used include the GABA agonist baclofen, diazepam and tizanidine (an Oj-adrenoceptor agonist). 

Krogsgaard-Larsen, P, Hjeds, H., Falch, E., Jprgensen, E. S., Nielsen, L. Recent advances in GABA agonists, antagonists and uptake inhibitors structure-activity relationships and therapeutic potential. In Advances in Drug Research (Testa, B., Ed.), Vol. 17. Academic Press London, 1988, pp. 381-456. 

Baclofen is considered a GABA agonist. The drug thus decreases afferent activity at the level of the spinal cord, resulting in a decrease in the release of glutamic acid and aspartic acid, and decreased activation of a-motor neurons. In addition, the drug mediates some CNS depression, particularly in large doses. This supraspinal action also contributes to muscle relaxation. 

---