In this study we have investigated the effect of withdrawal of morphine and the analogs on neuroblastoma cell line SH-SY-5Y after prolonged incubation with the drug. Morphine and some of its analogs induced a state of supersensitivity to forskolin-induced cyclic AMP formation in cells after prolonged incubation and withdrawal. Only those morphine analogs which are capable of producing physical dependence induced supersensitivity. Viminol, an analgesic that has been introduced in therapy in Europe some ten years ago was also tested in the system along with some newer derivatives of viminol. Only viminol analogs Z4349, Z4381 induced supersensitivity in neuroblastoma cell to a similar extent as morphine while Z4666 and Z4669 were not capable of inducing supersensitivity and therefore are incapable of inducing physical dependence. Tolerance to forskolin-induced cyclic AMP formation after prolonged incubation with morphine-like analgesics occur with all the drugs tested except Z4666. Cross-tolerance to morphine and viminol was induced when cells were preincubated with sufentanil for two days, while cross-tolerance to sufentanil did not occur when cells were preincubated with morphine or viminol. Moreover cross-tolerance to morphine occurred when cells were pretreated with all viminol analogs except for Z4666 and it occurred to all the derivatives except Z4666 when the cells were incubated with morphine.
