Antinociceptive and substance P antagonistic effects of intrathecally injected spantide II in rat: no signs of motor impairment or neurotoxicity.

The effect of intrathecally (i.t.) applied substance P (SP) analogue, (D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nle 11)-SP (Spantide II), was examined in rats. Spantide II even at a high dose (10 micrograms) did not evoke any behavioural responses and caused no motor disturbances, but it did have a brief antinociceptive effect on the hot-plate test. Spantide II dose-dependently reduced the caudally directed scratching/biting behaviour, evoked by 1 microgram i.t. SP for over 30 min, but did not block the caudally directed scratching behaviour evoked by i.t. somatostatin. Histological examination revealed no pathological changes in the spinal cord after treatment with Spantide II. The results indicate that Spantide II is an effective tachykinin antagonist in the central nervous system and that it causes no neural damage.