Tags

Type your tag names separated by a space and hit enter

Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain.
J Pharmacol Exp Ther. 2000 Aug; 294(2):444-50.JP

Abstract

CI-1021 ([(2-benzofuran)-CH(2)OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH (3))Ph) is a selective and competitive neurokinin-1 (NK(1)) receptor antagonist. This study examines its activity in animal models of inflammatory and neuropathic pain. In mice, CI-1021 (1-30 mg/kg, s.c.) dose dependently blocked the development of the late phase of the formalin response with a minimum effective dose (MED) of 3 mg/kg. Two chemically unrelated NK(1) receptor antagonists, CP-99,994 (3-30 mg/kg) and SR 140333 (1-100 mg/kg), also dose dependently blocked the late phase, with respective MEDs of 3 and 10 mg/kg. PD 156982, a NK(1) receptor antagonist with poor central nervous system penetration, failed to have any effect. However, when administered i. c.v., it selectively blocked the late phase of the formalin response. Chronic constrictive injury (CCI) to a sciatic nerve in the rat induced spontaneous pain, thermal and mechanical hyperalgesia, and cold, dynamic, and static allodynia. CI-1021 (10-100 mg/kg) and morphine (3 mg/kg) blocked all the responses except dynamic allodynia. Carbamazepine (100 mg/kg) was weakly effective against all the responses. Once daily administration of morphine (3 mg/kg, s. c.) in CCI rats led to the development of tolerance within 6 days. Similar administration of CI-1021 (100 mg/kg, s.c.) for up to 10 days did not induce tolerance. Moreover, the morphine tolerance failed to cross-generalize to CI-1021. CI-1021 blocked the CCI-induced hypersensitivity in the guinea pig, with a MED of 0.1 mg/kg, p.o. CI-1021 (10-100 mg/kg, s.c.) did not show sedative/ataxic action in the rat rota-rod test. It is suggested that NK(1) receptor antagonists possess a superior side effect profile to carbamazepine and morphine and may have a therapeutic use for the treatment of inflammatory and neuropathic pain.

Authors+Show Affiliations

Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10900217

Citation

Gonzalez, M I., et al. "Evaluation of Selective NK(1) Receptor Antagonist CI-1021 in Animal Models of Inflammatory and Neuropathic Pain." The Journal of Pharmacology and Experimental Therapeutics, vol. 294, no. 2, 2000, pp. 444-50.
Gonzalez MI, Field MJ, Hughes J, et al. Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. 2000;294(2):444-50.
Gonzalez, M. I., Field, M. J., Hughes, J., & Singh, L. (2000). Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain. The Journal of Pharmacology and Experimental Therapeutics, 294(2), 444-50.
Gonzalez MI, et al. Evaluation of Selective NK(1) Receptor Antagonist CI-1021 in Animal Models of Inflammatory and Neuropathic Pain. J Pharmacol Exp Ther. 2000;294(2):444-50. PubMed PMID: 10900217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain. AU - Gonzalez,M I, AU - Field,M J, AU - Hughes,J, AU - Singh,L, PY - 2000/7/20/pubmed PY - 2000/8/29/medline PY - 2000/7/20/entrez SP - 444 EP - 50 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 294 IS - 2 N2 - CI-1021 ([(2-benzofuran)-CH(2)OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH (3))Ph) is a selective and competitive neurokinin-1 (NK(1)) receptor antagonist. This study examines its activity in animal models of inflammatory and neuropathic pain. In mice, CI-1021 (1-30 mg/kg, s.c.) dose dependently blocked the development of the late phase of the formalin response with a minimum effective dose (MED) of 3 mg/kg. Two chemically unrelated NK(1) receptor antagonists, CP-99,994 (3-30 mg/kg) and SR 140333 (1-100 mg/kg), also dose dependently blocked the late phase, with respective MEDs of 3 and 10 mg/kg. PD 156982, a NK(1) receptor antagonist with poor central nervous system penetration, failed to have any effect. However, when administered i. c.v., it selectively blocked the late phase of the formalin response. Chronic constrictive injury (CCI) to a sciatic nerve in the rat induced spontaneous pain, thermal and mechanical hyperalgesia, and cold, dynamic, and static allodynia. CI-1021 (10-100 mg/kg) and morphine (3 mg/kg) blocked all the responses except dynamic allodynia. Carbamazepine (100 mg/kg) was weakly effective against all the responses. Once daily administration of morphine (3 mg/kg, s. c.) in CCI rats led to the development of tolerance within 6 days. Similar administration of CI-1021 (100 mg/kg, s.c.) for up to 10 days did not induce tolerance. Moreover, the morphine tolerance failed to cross-generalize to CI-1021. CI-1021 blocked the CCI-induced hypersensitivity in the guinea pig, with a MED of 0.1 mg/kg, p.o. CI-1021 (10-100 mg/kg, s.c.) did not show sedative/ataxic action in the rat rota-rod test. It is suggested that NK(1) receptor antagonists possess a superior side effect profile to carbamazepine and morphine and may have a therapeutic use for the treatment of inflammatory and neuropathic pain. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10900217/Evaluation_of_selective_NK_1__receptor_antagonist_CI_1021_in_animal_models_of_inflammatory_and_neuropathic_pain_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10900217 DB - PRIME DP - Unbound Medicine ER -