Effects of RPR 100893, a potent NK1 antagonist, on the jaw-opening reflex in the guinea pig

Abstract RPR 100893 appears as a new potent NK1 selective non-peptide antagonist both in vitro and in vivo, and exhibits high affinity for guinea pig and human NK1 receptor [M. Tabart, J.-F. Peyronel, Synthesis of RPR 100893, prototype of a new series of potent and selective non-peptide NK1 antagonists: the triarylperhydroisoindolols, Bioorg. Med. Chem. Lett., 4 (1994) 673–676.]. Intra-oral administration of RPR 100893 (3, 15, 10, 30 mg/kg) was performed in freely moving guinea pigs during recording of the short- (6–10 ms) and long-latency (18–26 ms) jaw-opening reflex (JOR) elicited by electrical stimulation (0.5 Hz) of the lower incisor tooth pulp. RPR 100893 induced a noticeable and dose-dependent increase of the long-latency reflex thresholds ( P P =0.14). The results suggest that, in guinea pigs, the long-latency JOR requires activation of NK1 receptors, while the earlier reflex component, elicited by activation of periodontal afferents, does not. These NK1 receptors could be located either on JOR interneurons activated by tooth pulp afferents or on digastric motoneurons, receiving the tooth pulp input through a polysynaptic pathway.