title: CNS drug development: lessons from the development of ondansetron, aprepitant, ramelteon, varenicline, lorcaserin, and suvorexant. Part I.
abstract: This column is the first in a two-part series exploring lessons for psychiatric drug development that can be learned from the development of six central nervous system drugs with novel mechanisms of action over the past 25 years. Part 1 presents a brief overview of the neuroscience that supported the development of each drug, including the rationale for selecting a) the target, which in each case was a receptor for a specific neurotransmitter system, and b) the indication, which was based on an understanding of the role that target played in a specific neural circuit in the brain. The neurotransmitter systems on which the development of these agents were based included serotonin for ondansetron and lorcaserin, dopamine for varenicline, substance P (or neurokinin) for aprepitant, melatonin for ramelteon, and orexin for suvorexant. The indications were chemotherapy-induced nausea and vomiting for ondansetron and aprepitant, smoking cessation for varenicline, weight loss for lorcaserin, and insomnia for suvorexant and ramelteon.
authors.affiliation: PRESKORN: University of Kansas School of Medicine-Wichita and Kansas University-Wichita Clinical Trials Unit.
authors.forename: Sheldon H
authors.initials: SH
authors.lastname: Preskorn
mesh_terms: D000077608:Aprepitant; D001381:Azepines / Q000266:history / Q000494:pharmacology*; D001552:Benzazepines / Q000266:history / Q000494:pharmacology*; D002491:Central Nervous System Agents; D055808:Drug Discovery / Q000266:history / Q000379:methods*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007192:Indenes / Q000266:history / Q000494:pharmacology*; D009025:Morpholines / Q000266:history / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000266:history / Q000502:physiology*; D017294:Ondansetron / Q000266:history / Q000494:pharmacology*; D011810:Quinoxalines / Q000266:history / Q000494:pharmacology*; D014230:Triazoles / Q000266:history / Q000494:pharmacology*; D000068580:Varenicline
chemical_list: D001381:Azepines; D001552:Benzazepines; D002491:Central Nervous System Agents; D007192:Indenes; D009025:Morpholines; D018377:Neurotransmitter Agents; D011810:Quinoxalines; D014230:Triazoles; C551624:suvorexant; D000077608:Aprepitant; D017294:Ondansetron; C506658:lorcaserin; C495910:ramelteon; D000068580:Varenicline