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 n ervous system (CNS) penetrant of tachykinin NK1 receptor antagonists w as investigated. Intracerebroventricular infusion of the highly select ive tachykinin NK1 receptor agonist GR73632 (3 pmol) induced a vigorou s repetitive hind foot tapping response which was inhibited by CP-99,9 94 (ID50 = 0.06 mg/kg i.v.) but not by its less active enantiomer, CP1 00,263 (10 mg/kg i.v.). Similarly, the poorly CNS penetrant quaternise d compound, L-743,310, failed to inhibit foot tapping at doses up to 3 mg/kg i.v. In contrast, all three compounds inhibited chromodacryorrh oea induced by systemic administration of GR73632 (0.5 nmol i.v.) (ID5 0 = 0.06, 2.95 and 0.004 mg/kg i.v., respectively). These findings con firm that foot tapping and chromodacryorrhoea in gerbils provide simpl e assays for the central and peripheral activation of tachykinin NK1 r eceptors.