Enantioselective inhibition of the formalin paw late phase by the NK1 receptor antagonist L-733,060 in gerbils

• Published in: Pain (Amsterdam) Vol. 67; no. 1; pp. 189 - 195
• Main Authors: RUPNIAK, N. M. J, CARLSON, E, BOYCE, S, WEBB, J. K, HILL, R. G
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.09.1996
• Subjects: Analgesics; Animals; Biological and medical sciences; Female; Foot; Formaldehyde - pharmacology; Gerbillinae; Injections; Male; Medical sciences; Motor Activity - drug effects; Neurokinin-1 Receptor Antagonists; Neuropharmacology; Nociceptors - drug effects; Nociceptors - physiology; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Piperidines - chemistry; Piperidines - pharmacology; Stereoisomerism; Substance P - analogs & derivatives; Substance P - antagonists & inhibitors; Substance P - pharmacology; Time Factors; Nociception; NK1 receptor; Rodentia; Central nervous system; Lower limb; Analgesia; Vertebrata; Chemotherapy; Mammalia; Analgesic; Treatment; Animal; Enantiomer; Antagonist; Gerbil
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/0304-3959(96)03109-0

Intravenous administration of the NK1 receptor antagonist L-733,060 to gerbils 3 h before intraplantar injection of formalin caused a dose-dependent and complete inhibition of the late, but not early, phase nociceptive response (paw licking). The ID50 for L-733,060 (0.17 mg/kg) revealed a greater than 50-fold separation in potency over its less active enantiomer L-733,061 (ID50 > or = 10 mg/kg). In contrast, the non-brain penetrant quaternary ketone NK1 receptor antagonist, L-743,310 (3 mg/kg), did not attenuate the response to formalin, indicating that the antinociceptive effect of blockade of NK1 receptors by L-733,060 in this assay is centrally-mediated. These findings add to the preclinical evidence that NK1 receptor antagonists may be of therapeutic use as centrally-acting analgesics.