Provides Mechanistic Rationale for the Clinical Findings that Cytisinicline (Cytisine) Treatment is Associated with Lower Rates of Nausea and Vomiting compared to Chantix
SEATTLE, Wash and VANCOUVER, British Columbia, September 18, 2020 — Achieve Life Sciences, Inc. (NASDAQ: ACHV), a clinical-stage pharmaceutical company committed to the global development and commercialization of cytisinicline for smoking cessation, today announced data presented at the Society for Research on Nicotine and Tobacco European (SRNT-E) Annual Meeting.
The presentation, “Cytisine’s Lower Potency at 5-HT3 Receptors May Explain its Lower Incidence of Nausea and Vomiting than Varenicline”, provides a rationale based on detailed receptor pharmacology to explain why the incidence of nausea and vomiting associated with cytisinicline appears to be consistently lower than that seen with varenicline.
The study, conducted at the University of Cambridge Department of Biochemistry by Professor Sarah Lummis and Dr. Kerry Price, was designed to examine the in vitro binding characteristics of cytisinicline compared to varenicline at the human 5-HT3 receptor. Using a radioligand antagonist displacement design, the study reported an IC50 of 0.50 mM for cytisinicline and 0.25 µM for varenicline, representing a 2000-greater fold agonist binding affinity to the 5-HT3 receptor for varenicline compared to cytisinicline.
“It is well-established that agonist activation of 5-HT3 receptors in the brain stem directly leads to nausea and vomiting. These data provide further rationale to explain what has been consistently observed in clinical studies reporting the adverse event profiles of cytisinicline and varenicline,” commented Achieve’s Chief Scientific Officer, Dr. Anthony Clarke. “Nausea and vomiting can greatly impact smoker’s compliance with medication, their willingness to complete the course of treatment, and ultimately, their ability to successfully quit smoking.”