Spinal blockade with intrathecal spiradoline and buprenorphine in rats

This study aimed to evaluate the spinal blockade effects of κ-opioid receptor ligands (spiradoline, U-50488H, and buprenorphine) compared with mepivacaine, and used isobolographic analysis to assess the interaction between spiradoline and mepivacaine. Rats received intrathecal injections of spiradoline, U-50488, buprenorphine, or mepivacaine, followed by neurobehavioral assessments of motor function and nociception. Spiradoline and mepivacaine were co-administered at a fixed dose ratio to assess their interaction using isobolographic analysis. We showed that intrathecal administration of spiradoline, U-50488, and buprenorphine induced spinal motor and nociceptive blockade at an equal concentration of 30 mM. In dose-dependent studies, spiradoline exhibited significantly greater potency (P < 0.01) than mepivacaine for spinal motor and nociceptive blockade. At equipotent doses (ED₂₅, ED₅₀, and ED₇₅), spiradoline produced a significantly longer duration of spinal motor and nociceptive blockade compared to mepivacaine (P < 0.001). Co-administration of spiradoline and mepivacaine resulted in an additive effect on spinal blockade of motor function and nociception. We concluded that spiradoline demonstrated the highest potency and most extended duration of action among drugs, whereas U-50488 and buprenorphine exhibited similar or lower potency than mepivacaine. Spiradoline elicited a longer duration of action than mepivacaine. The combination of spiradoline and mepivacaine produced an additive effect on spinal blockade, resembling the interaction observed with two local anesthetics.