The present invention aims to provide a novel low-molecular-weight compound having an orexin agonist activity, which is expected to be useful as a superior agent for the treatment or prophylaxis of narcolepsy. The present invention provides a compound showing superior orexin agonist activity which is represented by the formula (I) ##STR00001##
wherein each symbol is as defined in the DESCRIPTION, and a pharmaceutically acceptable acid addition salt thereof, as well as an orexin agonist containing the compound or a pharmaceutically acceptable acid addition salt thereof.

The invention relates to a time controlled, immediate release drug delivery system for oral administration of a first active ingredient to a subject in need thereof. The invention additionally relates to a dual drug delivery device, comprising the time controlled, immediate release drug delivery system according to the invention, further comprising a second coating comprising a second active ingredient.

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described.

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described.

Oral pharmaceutical solution comprising a pharmaceutically acceptable salt of lisdexamfetamine, and a pharmaceutically acceptable aqueous carrier comprising a buffer and a cosolvent selected from the group consisting of a glycol, a polyol, and a mixture thereof, wherein the pH of the solution is from 5.5 to 9.0. The oral pharmaceutical solution presents excellent physicochemical stability, even under alkaline conditions.

The invention provides certain nicotine salts, co-crystals, and salt co-crystals and provides novel polymorphic forms of certain nicotine salts. In particular, nicotine salts with mucic acid, 3,5-dihydroxybenzoic acid, and 2,3-dihydroxybenzoic acid, and crystalline polymorphic forms of nicotine 4-acetamidobenzoate, nicotine gentisate, and nicotine 1-hydroxy-2-naphthoate are described. The invention further provides methods of preparation and characterization of such nicotine salts, co-crystals, and salt co-crystals and polymorphic forms thereof. In addition, tobacco products, including smoking articles, smokeless tobacco products, and electronic smoking articles comprising nicotine salts, co-crystals, and/or salt co-crystals are also provided.

The present invention relates to the field of memory and cognitive functions. Here the inventors show that memory stimulations induce autophagy in the mouse hippocampus, while local pharmacological and genetic modulations of hippocampal autophagy strongly influence memory acquisition. More, the inventors observe that hippocampal autophagy declines during aging and they find that restoring autophagy specifically in the hippocampus of aged mice, following autophagy inducers (such as TAT-Beclin-1), can significantly reverse age-related memory decline. Their results reveal a novel physiological role of autophagy in regulating hippocampal-dependent memory functions, and demonstrate the potential therapeutic benefits of modulating autophagy in order to prevent and/or reverse the deleterious effects of aging on cognitive function. The present invention relates to an activator of the autophagy for use in the restoration and/or improvement of cognitive functions in a subject in need thereof.

The present invention relates to the field of memory and cognitive functions. Here the inventors show that memory stimulations induce autophagy in the mouse hippocampus, while local pharmacological and genetic modulations of hippocampal autophagy strongly influence memory acquisition. More, the inventors observe that hippocampal autophagy declines during aging and they find that restoring autophagy specifically in the hippocampus of aged mice, following autophagy inducers (such as TAT-Beclin-1), can significantly reverse age-related memory decline. Their results reveal a novel physiological role of autophagy in regulating hippocampal-dependent memory functions, and demonstrate the potential therapeutic benefits of modulating autophagy in order to prevent and/or reverse the deleterious effects of aging on cognitive function. The present invention relates to an activator of the autophagy for use in the restoration and/or improvement of cognitive functions in a subject in need thereof.

The invention relates to the use of Compound (I), as defined herein, or pharmaceutically acceptable salt thereof, in the treatment of excessive daytime sleepiness associated with Parkinson's disease.

The invention relates to the use of Compound (I), as defined herein, or pharmaceutically acceptable salt thereof, in the treatment of excessive daytime sleepiness associated with Parkinson's disease.