Behavioural assessment as substance P antagonists in mice.
A series of eleven undeca- and four hexapeptide antagonists of substance P (SP) have been assayed by the SP-induced behavioural test in mice. When 2 nmol of [D-Arg1, D-Pro, D-Trp, Leu]-SP (SP 1-11 I) was intrathecally injected together with SP (0.1 nmol), SP-induced response which consists of scratching, biting and licking was markedly inhibited. [D-Trp, Leu]-SP 6-11 (SP 6-11 I) given in a dose of 2 nmol was also inhibited the SP-induced response to the same degree as SP 1-11 I. Some of SP 1-11 or SP 6-11 analogues substituted with fluorine in positions 7 and/or 8 maintained the antagonistic effect of SP 1-11 I or SP 6-11 I, though the others were weaker. Intrathecal administration of SP 1-11 I and SP 6-11 I resulted in long-lasting antinociceptive effects as measured by the tail-flick test. Fluorine-containing SP analogues were less potent than the above two analogues in producing antinociception. These results suggest that the antagonistic effect of SP analogues on the SP-induced nociceptive response do not necessarily relate to antinociceptive activity at the spinal cord level.
D000698:Analgesia; D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000503:physiopathology; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000700:Analgesics; D013373:Substance P