Differential inhibition of foot tapping and chromodacryorrhoea in gerbils by CNS penetrant and non-penetrant tachykinin NK1 receptor antagonists.

The inhibition of GR73632-induced foot tapping in gerbils by central nervous system (CNS) penetrant of tachykinin NK1 receptor antagonists was investigated. Intracerebroventricular infusion of the highly selective tachykinin NK1 receptor agonist GR73632 (3 pmol) induced a vigorous repetitive hind foot tapping response which was inhibited by CP-99,994 (ID50 = 0.06 mg/kg i.v.) but not by its less active enantiomer, CP100,263 (10 mg/kg i.v.). Similarly, the poorly CNS penetrant quaternised compound, L-743,310, failed to inhibit foot tapping at doses up to 3 mg/kg i.v. In contrast, all three compounds inhibited chromodacryorrhoea induced by systemic administration of GR73632 (0.5 nmol i.v.) (ID50 = 0.06, 2.95 and 0.004 mg/kg i.v., respectively). These findings confirm that foot tapping and chromodacryorrhoea in gerbils provide simple assays for the central and peripheral activation of tachykinin NK1 receptors.