Provided are: a pyridazinone derivative and/or a pharmaceutically acceptable salt thereof, which is useful as a therapeutic agent and/or a prophylactic agent for diseases in which Nav1.1 is involved and various central nervous system diseases; and a medicine containing the pyridazinone derivative and/or the pharmaceutically acceptable salt thereof as an active ingredient. A compound represented by formula (1) or a pharmaceutically acceptable salt thereof.

##STR00001##

[In the formula, M.sup.1 represents a saturated or partially unsaturated C.sub.4-12 carbocyclic group or the like; R.sup.1 and R.sup.2 independently represent a hydrogen atom or the like; M.sup.2 represents a group represented by formula (2a) or the like; X.sup.1a, X.sup.1b and X.sup.1c independently represent N or the like; X.sup.2, X.sup.3 and X.sup.4 independently represent CR.sup.3 or the like; A.sup.1 and A.sup.2 independently represent N or the like; and R.sup.3 represents a hydrogen atom or the like.]

Compositions and methods are provided for modulating the activity of cells using engineered receptors, polynucleotide encoded engineered receptors, and gene therapy vectors comprising polynucleotides encoding engineered receptors. These compositions and methods find particular use in modulating the activity of neurons, for example in the treatment of disease or in the study of neuronal circuits.

Compositions and methods are provided for modulating the activity of cells using engineered receptors, polynucleotide encoded engineered receptors, and gene therapy vectors comprising polynucleotides encoding engineered receptors. These compositions and methods find particular use in modulating the activity of neurons, for example in the treatment of disease or in the study of neuronal circuits.

The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

Aspects of the present invention relate to a method of treating an epileptic encephalopathy in a mammal in need thereof, comprising administering a composition comprising an effective amount of (4-benzyl-4-hydroxypiperidin-1-yl) (2,4′-bipyridin-3-yl)methanone or a pharmaceutically acceptable salt thereof to the mammal.

Aspects of the present invention relate to a method of treating an epileptic encephalopathy in a mammal in need thereof, comprising administering a composition comprising an effective amount of (4-benzyl-4-hydroxypiperidin-1-yl) (2,4′-bipyridin-3-yl)methanone or a pharmaceutically acceptable salt thereof to the mammal.

The present application discloses pharmaceutical compositions and methods of treating neurological disorders and seizure disorders with the high dose modified release compositions of huperzine. The pharmaceutical compositions and methods described herein, allow for higher dosing of huperzine, while avoiding rapid peak plasma levels, thereby avoiding the dose-limiting adverse events associated with the immediate release formulations.

The present application discloses pharmaceutical compositions and methods of treating neurological disorders and seizure disorders with the high dose modified release compositions of huperzine. The pharmaceutical compositions and methods described herein, allow for higher dosing of huperzine, while avoiding rapid peak plasma levels, thereby avoiding the dose-limiting adverse events associated with the immediate release formulations.

Provided herein are 2-amino-pyrazolyl-[1,2,4]triazolo [1,5a]pyridine derivatives. Such compounds are useful, for example, for the treatment and/or prevention of neurodegenerative diseases or disorders such as ophthalmological neurodegenerative disorders. This disclosure also features compositions containing the same as well as methods of using and making the same.

The present discloses relates to a composition, a kit or a method using an eIF4E inhibitor for diagnosis or treatment of a condition associated with increased activity of eIF4E.