First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288

• Published in: Journal of psychopharmacology (Oxford) Vol. 31; no. 4; p. 434
• Main Authors: Gee, Kelvin W, Olincy, Ann, Kanner, Richard, Johnson, Lynn, Hogenkamp, Derk, Harris, Josette, Tran, Minhtam, Edmonds, Stephen A, Sauer, William, Yoshimura, Ryan, Johnstone, Timothy, Freedman, Robert
• Format: Journal Article
• Language: English
• Published: United States 01.04.2017
• Subjects: Adult; Allosteric Regulation - drug effects; alpha7 Nicotinic Acetylcholine Receptor - metabolism; Anilides - adverse effects; Anilides - pharmacokinetics; Anilides - therapeutic use; Biomarkers - metabolism; Cognition - drug effects; Double-Blind Method; Female; Humans; Isoxazoles - adverse effects; Isoxazoles - pharmacokinetics; Isoxazoles - therapeutic use; Male; Neurocognitive Disorders - drug therapy; Neurocognitive Disorders - metabolism; Nicotine - administration & dosage; Nicotinic Agonists - adverse effects; Nicotinic Agonists - pharmacokinetics; Nicotinic Agonists - therapeutic use; Receptors, Nicotinic - metabolism; Schizophrenia - drug therapy; Schizophrenia - metabolism; Synaptic Transmission - drug effects; Young Adult; Receptors; drug evaluation; schizophrenia; cognition; nicotinic; allosteric modulators

Type I positive allosteric modulators (PAMs) of the alpha7-nicotinic receptor enhance its cholinergic activation while preserving the spatiotemporal features of synaptic transmission and the receptor's characteristic rapid desensitization kinetics. Alpha7-nicotinic receptor agonists have shown...