Abstract
α2 adrenergic receptors (ARs) are involved in many physiological processes, including mediating the antiepileptic effects of the catecholamine norepinephrine (NE). We generated data from agonists of α2 ARs. We hypothesized the performance of catecholamines to be higher than synthetic compounds of imidazolines and guanidines. Using extracellular recordings in the hippocampal CA3 region of rat brain slices, antiepileptiform actions of agonists of these chemical classes were recorded. Variations of the potency and efficacy of the agonists were considered with the parameters of their structural differences. Agonist classifications (full vs. partial) were based on relative efficacy to the endogenous neurotransmitter NE. Results indicated that catecholamines were full agonists. Among imidazolines and guanidines, UK‐14303 was the most efficacious. These results confirm our hypothesis that catecholamines were more efficacious. However, imidazolines and guanidines had higher potencies. Since differences in structures between catecholamines were trivial while structural differences among classes of agonist were significant, conclusions can be drawn that structural attributes of catecholamines contribute to their efficacy and potency at inhibiting hippocampal epileptiform activity. Supported by NSF ND EPSCoR, NSF CAREER, NSF REU Site, NIH, Epilepsy Foundation, American Physiological Society.
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