The present invention relates to compounds of formula (I): ##STR00001##
or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

The present invention relates to compounds of formula (I): ##STR00001##
or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

A tertiary amine pharmaceutical composition includes a drug having a tertiary amine structure, a biocompatible polymer material, and a quaternary ammonium salt impurity. The pharmaceutical composition is obtained by dissolving or dispersing the drug in a halogenated hydrocarbon or a mixed solvent mainly containing halogenated hydrocarbon or a solution containing halogenated hydrocarbon. The quaternary ammonium salt impurity is generated from reacting the drug having the tertiary amine structure with the halogenated hydrocarbon. The pharmaceutical composition comprises 40 wt % to 80 wt % of the biocompatible polymer material, and 20 wt % to 60 wt % of the drug with the tertiary amine structure. The content of the quaternary ammonium salt impurity is less than 0.05 wt %, the content of the halogenated hydrocarbon in the composition is less than 1.5 wt %, and the quaternary ammonium salt impurity does not increase or increases slowly during storage, which complies with requirements of pharmaceutical regulations.

The present invention provides a composition which comprises a compound which is a mixture of deuterium containing and non-deuterium containing molecules having the structure:

##STR00001## wherein R.sub.1 is

##STR00002## wherein at least one of H.sub.1, H.sub.2 or H.sub.3 is a deuterium-enriched —H site, or

##STR00003## wherein at least one of H.sub.1, H.sub.2, H.sub.3, H.sub.4 or H.sub.5 is a deuterium-enriched —H site,
or a pharmaceutically acceptable salt of the compound, and methods of using the composition to treat pain, depressive disorders, mood disorders, anxiety disorders, opioid use disorders, and opioid withdrawal symptoms.

The present invention provides a composition which comprises a compound which is a mixture of deuterium containing and non-deuterium containing molecules having the structure:

##STR00001## wherein R.sub.1 is

##STR00002## wherein at least one of H.sub.1, H.sub.2 or H.sub.3 is a deuterium-enriched —H site, or

##STR00003## wherein at least one of H.sub.1, H.sub.2, H.sub.3, H.sub.4 or H.sub.5 is a deuterium-enriched —H site,
or a pharmaceutically acceptable salt of the compound, and methods of using the composition to treat pain, depressive disorders, mood disorders, anxiety disorders, opioid use disorders, and opioid withdrawal symptoms.

The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABA.sub.A agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABA.sub.A receptor in dorsal root ganglion neurons in the subject using a vector.

The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABA.sub.A agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABA.sub.A receptor in dorsal root ganglion neurons in the subject using a vector.

Methods are described to reduce risk of or prevent wooden chest syndrome or other respiratory effects arising from exposure to fentanyl or a fentanyl analog, for instances inpatients receiving medically assisted treatment (MAT) for Opioid Use Disorder (OUD) or who are receiving analgesia and pain management with F/FAs. Pharmaceutical compositions for use in such methods are described.

Methods are described to reduce risk of or prevent wooden chest syndrome or other respiratory effects arising from exposure to fentanyl or a fentanyl analog, for instances inpatients receiving medically assisted treatment (MAT) for Opioid Use Disorder (OUD) or who are receiving analgesia and pain management with F/FAs. Pharmaceutical compositions for use in such methods are described.

This invention relates to novel method of treating or ameliorating a retinal disease or disorder or retinal degradation in a subject and a novel method of restoring retinal pigment epithelium cell compromising the administration of a one or more compounds which modulate Nox4, formation of radical oxygen species, serine protease, a dopamine receptor, NF-kB, mTOR, AMPK, RPE epithelial to mesenchymal transition, RPE dedifferentiation, or one or more Rho GTPases; and kits for administration of the methods.