Table 1.

Potential mechanisms underlying DOR-dependent neuroprotection.

Ischemic Cascade Event	DOR-Dependent Action	Key Features	References
Mitochondrial Depolarization	K_ATP channel activation	Protects cultured cortical neurons against NaN₃;reduces NaN₃-induced downregulation of DOR.	64
Na⁺ influx	Decreases Na⁺ influx	Blocks voltage-gated Na⁺ channels and reduces Na⁺ influx via NMDA channels in cortical slices exposed to anoxia.	65,66
K⁺ Efflux	Decreases K⁺ efflux	Attenuates K⁺ efflux from cortical slices exposed to anoxia or OGD via PKC-dependent, PKA-independent pathway.	67,68
K⁺ Efflux	Decreases K⁺ efflux	Inhibition of Ca²⁺ influx reduces activation of Ca²⁺-activated K⁺ (BK) channels in cortical slices exposed to anoxia.	68
Ca²⁺ influx	Decreases Ca²⁺ influx	Indirect evidence of reduced Ca²⁺ influx cortical slices exposed to anoxia.	68
Ca²⁺ influx	Decreases Ca²⁺ influx	Hypoxia-induced Ca²⁺ influx reduced in adrenal medulla cells by decreasing voltage-gated Ca²⁺ currents.	69
Increased Glutamate Release	Inhibits glutamate release presynaptically	Decreased amplitude of AMPA EPSCs/EPSPs in lamina II of lumbar spinal cord slices without altering responses to pressure-ejected AMPA.	70
Increased Glutamate Release	Inhibits glutamate release presynaptically	Decreased frequency, but not amplitude, of mEPSCS in amygdala slices.	71
Increased AMPA and NMDA Receptor Activation	Decreases NMDA-dependent currents	Reduces Na⁺ influx via NMDA channels in cortical slices exposed to anoxia.	66
Increased AMPA and NMDA Receptor Activation	Decreases NMDA-dependent currents	Reduces NMDA currents during anoxia in turtle cortical slices.	32
Increased Free Radical Production	Decreases free radical release or impact	Hypoxic preconditioning attenuates decrease in antioxidant scavengers and increase in oxidant proteins via DOR-dependent mechanism in retinal cells.	39
		DOR agonist drug acts as free radical scavenger.	72
		DOR agonist and plasma from hibernating woodchuck reduces NO release in microglia cell culture via DOR mechanism	29