ABSTRACT
Aim To provide scientific evidence for clinical drug combination by exploring the analgesic effect of aspirin combined with Kv7 channel openers, retigabine and flupirtine. Methods The mice were randomly divided into control group, aspirin group, flupirtine group, retigabine group, aspirin + flupirtine group and aspirin + retigabine group. To assess the antinociceptive effects of each group, the acetic acid-induced abdominal constriction test and the hot-plate test were used. Results In the acetic acid-induced abdominal constriction test, compared to aspirin group, the amount of abdominal constriction in aspirin + flupirtine group was significantly reduced (P <0.01). The latent period of abdominal constriction in aspirin + retigabine group was significantly prolonged ( P < 0. 01) and the number of abdominal constriction was significantly reduced (P < 0. 01). In the hot-plate test, compared to aspirin group, the increment percentage of latent period in aspirin + flupirtine group and aspirin + retigabine group showed an increased trend. Among them, the increment percentage of latent period 30 and 60 minutes after injections in aspirin + retigabine group had a significant difference from that in aspirin group (P <0. 05). Conclusion Kv7 channel openers, retigabine and flupirtine, can enhance the analgesic effect of aspirin.
ABSTRACT
The KCNQ gene family encodes five Kv7 channel sub-units(Kv7. 1-5) and four of these (Kv7. 2-5) channels are ex-pressed in the central nervous system ( CNS ) . Neuronal Kv7 channels participate in both pre-and post-synaptic modulation of neurotransmissions. Activation of neuronal Kv7 channels inhibits neuronal excitability and limits the release of monoaminergic neu-rotransmitter. Kv7 channel openers provide novel therapeutic op-tions in the treatment of disease states characterized by overactiv-ity of monoaminergic neurons ( e. g. schizophrenia, anxiety and drug abuse) . This review summarizes the studies on expression and functional role of Kv7 channels in monoaminergic neurotrans-mission in the CNS and the potential therapeutic effect of Kv7 channel openers on the disease characterized by overactivity of monoaminergic neurons.