With the help of extrinsic fluorescence quenching, it was demonstrated that venlafaxine is able to bind to the extracellular S1S2 domain of the NR1-1b subunit of the NMDA receptor, but not in clinically relevant concentrations. It was shown that venlafaxine takes part in maintaining NMDA receptors, and upregulating Grin2a and Grin2b expression. Venlafaxine treatment upregulated GRIA3 gene (glutamate receptor AMPA 3).
The anti-inflammatory effect of venlafaxine in the rat model of carrageenan-induced paw oedema was studied. It was shown that intraperitoneal and intracerebroventricular administration of the drug inhibited paw oedema, reduced myeloperoxidase activity, and decreased interleukin (IL)-1β and tumour necrosis factor (TNF)-α production.
Venlafaxine induced a dose-dependent antinociceptive effect, which was abolished by naloxone, norbinaltorphimine (κ-opioid receptor antagonist) and naltrindole (δ-opioid receptor antagonist), but not by beta-funaltrexamine (μ-opioid receptor antagonist). The authors suggested the involvement of κ- and δ-opioid mechanisms in an analgesic action of venlafaxine.