title: Comparative analysis of pharmacological treatments with N-acetyl-DL-leucine (Tanganil) and its two isomers (N-acetyl-L-leucine and N-acetyl-D-leucine) on vestibular compensation: Behavioral investigation in the cat.
abstract: Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-dl-leucine is a drug prescribed in clinical practice for the symptomatic treatment of acute UVL patients. The present study investigated the effects of N-acetyl-dl-leucine on the behavioral recovery after unilateral vestibular neurectomy (UVN) in the cat, and compared the effects of each of its two isomers N-acetyl-L-leucine and N-acetyl-D-leucine. Efficacy of these three drug treatments has been evaluated with respect to a placebo group (UVN+saline water) on the global sensorimotor activity (observation grids), the posture control (support surface measurement), the locomotor balance (maximum performance at the rotating beam test), and the spontaneous vestibular nystagmus (recorded in the light). Whatever the parameters tested, the behavioral recovery was strongly and significantly accelerated under pharmacological treatments with N-acetyl-dl-leucine and N-acetyl-L-leucine. In contrast, the N-acetyl-D-leucine isomer had no effect at all on the behavioral recovery, and animals of this group showed the same recovery profile as those receiving a placebo. It is concluded that the N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar (and even better) to that observed under treatment with the racemate component only.
authors.affiliation: Laboratoire de Neurosciences Intégratives et Adaptatives, UMR 7260; FR - Comportement, Cerveau, Cognition (Behavior, Brain, and Cognition), Aix-Marseille Université - CNRS, Centre Saint-Charles, Case B, 3 Place Victor Hugo, 13331 Marseille cedex 03, France. Electronic address: brahim.tighilet@univ-amu.fr.
authors.forename: Brahim
authors.initials: B
authors.lastname: Tighilet
authors.affiliation: Laboratoire de Neurosciences Intégratives et Adaptatives, UMR 7260; FR - Comportement, Cerveau, Cognition (Behavior, Brain, and Cognition), Aix-Marseille Université - CNRS, Centre Saint-Charles, Case B, 3 Place Victor Hugo, 13331 Marseille cedex 03, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Leonard
authors.affiliation: Laboratoire de Neurosciences Intégratives et Adaptatives, UMR 7260; FR - Comportement, Cerveau, Cognition (Behavior, Brain, and Cognition), Aix-Marseille Université - CNRS, Centre Saint-Charles, Case B, 3 Place Victor Hugo, 13331 Marseille cedex 03, France; Service ORL et de Chirurgie cervico-faciale Hôpital de la Conception Marseille, 147 Boulevard Baille, 13005 Marseille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bernard-Demanze
authors.affiliation: Laboratoire de Neurosciences Intégratives et Adaptatives, UMR 7260; FR - Comportement, Cerveau, Cognition (Behavior, Brain, and Cognition), Aix-Marseille Université - CNRS, Centre Saint-Charles, Case B, 3 Place Victor Hugo, 13331 Marseille cedex 03, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Lacour
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D002415:Cats; D007536:Isomerism; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009759:Nystagmus, Pathologic / Q000503:physiopathology; D004856:Postural Balance / Q000187:drug effects; D014722:Vestibule, Labyrinth / Q000187:drug effects* / Q000502:physiology* / Q000503:physiopathology
chemical_list: D007930:Leucine; C088117:acetylleucine
keywords: Behavioral recovery; Cat; Isomers l and d; Locomotor balance; N-acetyl-dl-leucine; Posture; Spontaneous vestibular nystagmus; Unilateral vestibular neurectomy