1 The modulatory actions of nociceptin/orphanin FQ on excitatory synaptic transmission were studied in super®cial dorsal horn neurones in transverse slices from 7 to 14 day old rats. 2 Glutamatergic excitatory postsynaptic currents (e.p.s.cs) were recorded from the somata of the neurones in the whole-cell patch-clamp con®guration. E.p.s.cs were evoked by extracellular electrical stimulation (100 ms, 3 ± 10 V) of the ipsilateral dorsal root entry zone by use of a glass electrode. E.p.s.cs with constant short latency (52.3 ms) and with no failures upon stimulation were assumed to be monosynaptic. These e.p.s.cs occurred with an average latency of 1.72+0.098 ms and exhibited a fast decay with a time constant, t, of 4.8+0.53 ms (n=30). 3 Nociceptin reversibly reduced the amplitudes of e.p.s.cs in a concentration-dependent manner in 25 out of 27 cells tested. Average maximum inhibition was 51.6+5.7% (mean+s.e.mean; n=9), at concentrations 43 mM. EC 50 was 485+47 nM and the Hill coecient was 1.29+0.09. 4 Inhibition of synaptic transmission by nociceptin (10 mM) was insensitive to the non-speci®c opioid receptor antagonist naloxone (10 mM) indicating that nociceptin did not act via classical opioid receptors. 5 In order to determine the site of action of nociceptin spontaneous miniature e.p.s.cs (m-e.p.s.cs) were recorded. Nociceptin reduced the frequency of m-e.p.s.cs in 6 out of 7 cells but had no eect on their amplitude distribution or on their time course. These ®ndings suggest a pre-rather than a postsynaptic modulatory site of action. This is in line with the ®nding that current responses elicited by extracellular application of L-glutamate (10 mM) were not aected by nociceptin (10 mM; n=7). 6 No positive correlation was found between the degree of inhibition by nociceptin (10 mM) and by the mixed d-and m-receptor agonist methionine-enkephalin (10 mM). This suggests that both neuropeptides acted on dierent but perhaps overlapping populations of synaptic connections. 7 Our results indicate that nociceptin inhibits excitatory synaptic transmission in the super®cial layers of the rat dorsal horn by acting on presynaptic, presumably ORL 1 receptors. This may be an important mechanism for spinal sensory information processing including nociception.

The aims of this study were to investigate the dose-dependent effects of spinally delivered nociceptin (0.3, 1, 3.3 and 10 nmol) on flinching behaviour in the rat formalin test and whether these effects were influenced by the concomitant systemic administration of naloxone (3 mg/kg, i.p.). The effect of the highest nociceptin dose differed statistically from vehicle, 0.3 and 1 nmol nociceptin. Following the administration of 1, 3.3 or 10 nmol nociceptin mean total flinches decreased dose-dependently. The effects of 10 nmol nociceptin were not reversed by a high dose of naloxone. We observed a decrease in flinching behaviour with intrathecally to the lumbar enlargement delivered nociceptin and conclude that nociceptin has antinociceptive effects in the rat formalin test.

We studied the influence of an add-on medication with oxcarbazepine on the cyclosporine trough level in a kidney transplant recipient with pharmacoresistant epilepsy. Two weeks after the beginning of the trial we observed a decrease of the cyclosporine trough and the Na serum levels. Both could be corrected by a small-dose reduction of oxcarbazepine, an augmentation of the cyclosporine dosis, and oral sodium chloride substitution. After this episode the cyclosporine trough and the Na serum levels remained stable. Seizure frequency was reduced by 95%. The influence of oxcarbazepine on the cyclosporine serum level has to be studied carefully in other patients after transplantation before the use of oxcarbazepine can be recommended in patients with an immunosuppressive medication with cyclosporine. Our data suggest that oxcarbazepine may be an effective drug with tolerable side effects in this group of patients.

No abstract