Inhibitory effects of a selective endothelin-A receptor antagonist YM598 on endothelin-1-induced potentiation of nociception in formalin-induced and prostate cancer-induced pain models in mice.

Abstract

In some diseases in which endothelin-1 (ET-1) production increases (e.g. prostate cancer), ET-1 is considered to be involved in the generation of pain. In the present study, we investigated the effects of a selective endothelin-A receptor antagonist, YM598, on the nociception potentiated by ET-1 in formalin-induced and cancer inoculation-induced pain models in mice. The formalin-induced pain model was prepared by intraplantar injection of 0.7% formalin into the hind paws of ICR mice, and the cancer pain model was prepared by inoculation of the human prostate cancer cell line PPC-1 into the hind paws of severe combined immunodeficiency mice. Formalin caused a biphasic pain response and paw edema in the mouse hind paw. ET-1 (10 pmol/paw) potentiated these responses, and single oral administration of YM598 (0.3-3 mg/kg) significantly inhibited this ET-1-induced potentiation of nociception and paw edema. ET-1 (10 pmol/paw) also potentiated the pain response in prostate cancer-inoculated mice. Both YM598 and atrasentan (0.3-3 mg/kg) significantly inhibited the ET-1-induced potentiation of nociception. These results suggest that selective endothelin-A receptor antagonists relieve pain in patients with various diseases in which ET-1 production increases (e.g. prostate cancer).

• Authors: Hironori Yuyama, Akiko Koakutsu, Noriko Fujiyasu, Akira Fujimori, Shuichi Sato, Kumiko Shibasaki, Shohei Tanaka, Katsumi Sudoh, Masao Sasamata, Keiji Miyata
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 44 Suppl 1 Pg. S479-82 (Nov 2004) ISSN: 1533-4023 [Electronic] United States
• PMID: 15838353 (Publication Type: Journal Article)

Chemical References

• Analgesics, Non-Narcotic
• Endothelin A Receptor Antagonists
• Endothelin-1
• N-(6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl)-2-phenylethenesulfonamide
• Pyrimidines
• Receptor, Endothelin A
• Sulfonamides
• Formaldehyde

Topics

• Administration, Oral
• Analgesics, Non-Narcotic (administration & dosage, pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Cell Line, Tumor
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Endothelin A Receptor Antagonists
• Endothelin-1 (metabolism)
• Formaldehyde
• Humans
• Male
• Mice
• Mice, Inbred ICR
• Mice, SCID
• Pain (etiology, metabolism, prevention & control)
• Pain Measurement
• Prostatic Neoplasms (complications, drug therapy, metabolism)
• Pyrimidines (administration & dosage, pharmacology)
• Receptor, Endothelin A (metabolism)
• Sulfonamides (administration & dosage, pharmacology)
• Time Factors