Behavioural and antinociceptive effects of intrathecally injected substance P analogues in mice.
The antinociceptive effects and antagonism of substance P (SP)-induced behaviour were examined after intrathecal injections in mice. When coadministered with SP, the SP analogues attenuated the SP-induced behaviour to various extents with [D-Arg1,D-Pro2,4,D-PHe7,D-His9]SP as the most potent antagonist. Physalaemin and eledoisin brought about a SP-like behavioural response. [D-Arg1,D-Trp7,9,Leu11]SP inhibited the response to eledoisin but not that to physalaemin. The SP analogues substituted with D-Trp7,9 and with Leu or Val in position 11 produced the strongest antinociceptive effects. Pretreatment with naloxone (5 mg/kg, i.p.) abolished the antinociceptive effects of [D-Trp7,9,Leu11]SP, implying that opiate receptors in the spinal cord mediate at least in part the antinociceptive effects. Animals under pentobarbital anesthesia showed a potentiated antinociceptive effect in the tail-flick test. In conclusion, we found that the SP analogues tested exerted varying degrees of antinociception, and that this was probably at least in part mediated by activation of spinal opiate receptors, whereas the behavioural antagonism was probably due to the blockade of spinal SP receptors.
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D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D015320:Tachykinins
D000700:Analgesics; D009419:Nerve Tissue Proteins; D015320:Tachykinins; D013373:Substance P; D009270:Naloxone