Abstract: Objective To study the effect of M1 and M3 receptors’ antagonists on the inhibition of delayed rectifier potassium current ( IK ) by nociceptin/orphanin FQ ( N/OFQ ) in acutely dissociated rat cerebral parietal cortical neurons. Methods Using whole-cell patch-clamp technique, recording effects of different subtypes of M receptor on the inhibition of IK by N/OFQ in rat cerebral cortical neurons. Results ( 1 ) N/OFQ inhibited IK in acutely dissociated rat cerebral parietal cortical neurons, and the inhibition rate was ( 30.8±5.6 )% ( P < 0.01 ); ( 2 ) PIR M1 receptor antagonist antagonized the inhibitory effect of N/OFQ on IK and the drop of currents varied from the control value of ( 30.8±5.6 )% to ( 15.5±2.5 )% ( P < 0.05 ); ( 3 ) M3 receptor antagonist 4DAMP has not obvious effects on the inhibitory effect of N/OFQ on IK. Conclusion M1-receptor involved in the inhibition of N/OFQ on IK in acutely dissociated rat cerebral parietal cortical neurons.