Changes in nociception after acute and chronic administration of zimelidine: different effects in the formalin test and the substance P behavioural assay.

The selective inhibitor of the reuptake of 5-hydroxytryptamine (5-HT), zimelidine, was administered intraperitoneally to mice (10 mg/kg) and nociceptive sensitivity was evaluated using the formalin test (20 microliters of 1% formalin, injected subcutaneously) and the assay for substance P (5 ng administered intrathecally). Zimelidine increased the behavioural response to formalin, but reduced the response to substance P. These effects of zimelidine seemed to be unchanged after chronic treatment (2 X 10 mg/kg for 14 days). It is suggested that zimelidine produces a central antinociceptive effect, but elicits a peripheral hyperalgesia, which predominates in the formalin test.