<Originals>Enhancement of fentanyl, clonidine and serotonin antinociceptive effects by diltiazem in spinal cord of rats
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概要
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Intracellular and extracellular movement of calcium ions regulate neuronal excitability and releases of neurotransmitters in the central nervous system (CNS). The current study was designed to investigate the antinociceptive effects of intrathecal (i.t.) co-administrations of fentanyl (μ-agonists), clonidine (α_2-adrenergic agonist) or 5-HT (serotonergic agonist) with diltiazem (a calcium-channel blocker) in rats. Antinociceptive effects were assessed with the tail-flick test. Although higher i.t. doses of fentanyl, clonidine or 5-HT respectively produced a significant antinociceptive effect, lower i.t. doses did not affect the noxious response. When similarly treated, diltiazem alone (100,200 μg) failed to suppress the nociceptive effects. However, concomitant administrations of antinociceptively inactive doses of fentanyl (1.0 μg), clonidine (2.5 μg) or 5-HT (25 μg) with diltiazem (200 μg) elicited significant suppressions on the thermonociceptive response accordingly. Furthermore, suppressive effects induced by subanalgesic doses of fentanyl, clonidine, or 5-HT, and diltiazem were significantly blocked by naloxone (μ-antagonist), yohimbine (α_2-adrenergic antagonist) and methysergide (serotonergic antagonist) respectively. Therefore, it is considered that diltiazem may significantly enhance the antinociceptive effect of each agent. These findings suggest that the calcium channel plays an important role in the antinociceptive effects in the spinal cord of rats.
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