GR-205171 (Glaxo Wellcome plc)

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Glaxo Wellcome is developing GR-205171, a neurokinin-1 (NK1) receptor antagonist.
• NK1 antagonists are being investigated for various medical applications.
• GR-205171 exhibits comparable affinity to the NK1 receptor as CP-99994.

Purpose of the Study:

• To evaluate the efficacy of GR-205171 in treating chemotherapy- and radiotherapy-induced emesis.
• To assess GR-205171's potential for managing post-operative nausea and emesis, and migraine.
• To explore the therapeutic utility of GR-205171 in inflammatory pain conditions.

Main Methods:

• Phase II clinical trials were initiated for the aforementioned indications.
• A combination trial involving GR-205171 and ondansetron was conducted.
• Preclinical studies assessed GR-205171's efficacy in animal models for emesis and pain.

Main Results:

• The combination of GR-205171 and ondansetron proved highly effective in preventing acute cisplatin-induced emesis.
• All patients receiving high-dose GR-205171 plus ondansetron achieved complete response.
• The combination achieved complete nausea control within 16 hours in 10 of 12 patients.
• GR-205171 demonstrated an ED90 of 0.03 mg/kg against radiation-induced emesis in ferrets.
• GR-205171 showed activity against adjuvant-induced inflammatory pain in rats.

Conclusions:

• GR-205171, in combination with ondansetron, is a highly effective treatment for chemotherapy-induced emesis.
• GR-205171 shows promise for managing various forms of emesis and potentially chronic inflammatory pain.