ZAPA is an isothiouronium analogue of gamma-aminobutyric acid (GABA) and a selective agonist of the low affinity GABA|A|receptor. Derivatives of ZAPA were studied for GABA|A|agonist activity and ZAPA, containing what is shown to be a crucial cis-double bond, demonstrated the highest affinity of its derivatives. ZAPA also shows higher affinity at GABA|A|than both the potent agonist muscimol and GABA itself. Perturbation of the GABA|A|system by chemicals such as ZAPA allows elucidation of its functions and presents an avenue of chemical intervention into neuronal signaling.
