Penehyclidine hydrochloride protects against oxygen and glucose deprivation injury by modulating amino acid neurotransmitters release.

Penehyclidine hydrochloride (PHC) is an anticholinergic agent, with only high degree of selectivity for M1 and M3 receptor subtypes. In this study, we investigated whether PHC could play a protective effect on hippocampal slice against oxygen and glucose deprivation (OGD), as well as related to the change of amino acid neurotransmitters release. Penehyclidine hydrochloride 2, 10, and 50 μM doses were adopted in the lactate dehydrogenase (LDH) leakage assay and triphenyl tetrazolium chloride (TTC) staining. The spontaneous miniature excitatory postsynaptic currents (mEPSCs) and amino acid neurotransmitters were detected by electrophysiology method and high-performance liquid chromatography (HPLC), respectively. Our study showed that PHC can lessen the LDH leakage ratio and tissue injury values according to TTC staining. Penehyclidine hydrochloride decreased the content of aspartate acid (Asp) and glutamate (Glu), and elevated the content of glycine (Gly) and gamma-aminobutyric acid (GABA). Ischemia increased the amplitude and frequency of the mEPSCs, but PHC obviously decreased the frequency and amplitude of mEPSCs. Thus, the study reveals the fact that PHC protects hippocampus slice against OGD injury by decreasing excitatory amino acids release and increasing inhibitory amino acids release.