Potential Application of FSNY-1 as Smoking Cessation Drug

Purpose: Varenicline, an FDA-approved drug, is effective in the treatment of nicotine addiction. However, varenicline has been shown to cause central nervous system effects in greater than 10% of users. The purpose of this study was to develop alternative treatments with potentially less side effects. Methods: A novel compound, FSNY-1 was tested for its ability to inhibit biphasic psychomotor stimulant and depressant effects of nicotine in mice. Different groups of young mice were pretreated with FSNY-1 (5, 10 mg/kg), or: varenicline (3 mg/kg), mecamylamine (2.5 mg/kg), or hexamethonium (3 mg/kg) prior to nicotine injection, and placed into chambers for recording locomotor activity for 120 minutes. Results: FSNY-1 and hexamethonium selectively blocked the stimulant phase of nicotine effects. Mecamylamine attenuated the stimulant and depressant phases of nicotine's action. Although varenicline blocked the stimulant effect of nicotine, it had a depressant effect when administered alone. FSNY-1 alone had neither a stimulant nor depressant effect. Conclusion: Based on these results, it can be predicted that FSNY-1 will be useful in the treatment of nicotine addiction without side effects associated with varenicline. It is significant that hexamethonium, which does not cross the blood-brain barrier, had a profile identical to FSNY-1. This supports the conclusion that ability to block autonomic outflow may be sufficient condition for clinical efficacy. Thus, inhibition of peripheral actions of nicotine may represent a significant target for new drug development. Additional studies will be needed to further test therapeutic potential of FSNY-1.