The disclosures herein relate to novel compounds of formula ##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 and n are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of inflammation, neurological or psychiatric disorders associated with modulating mGlu5 receptor function.

Herein is reported an anti-transferrin receptor antibody that specifically binds to human transferrin receptor and cynomolgus transferrin receptor, which comprises i) a humanized heavy chain variable domain derived from the heavy chain variable domain of SEQ ID NO: 01, and ii) a humanized light chain variable domain derived from the light chain variable domain of SEQ ID NO: 26, wherein the antibody has an off-rate for the human transferrin receptor that is equal to or less than (i.e. at most) the off-rate of the anti-transferrin receptor antibody 128.1 for the cynomolgus transferrin receptor, whereby the off-rates are determined by surface plasmon resonance, and whereby the anti-transferrin receptor antibody 128.1 has a heavy chain variable domain of SEQ ID NO: 64 and a light chain variable domain of SEQ ID NO: 65.

The present disclosure provides compounds and methods of use thereof for treating inflammatory diseases or disorders.

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein -------, R.sup.1, R.sup.2, R.sup.5, A and L are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia. ##STR00001##

The present invention relates to a method of treating or preventing a neurological condition mediated by a tau-dependent signalling complex in neurons of a subject, comprising treating the subject to: (a) promote phosphorylation of one or more amino acids residues of tau, wherein the phosphorylation of the amino acid residues causes disruption of the tau-dependent signalling complex in neurons of the subject; or (b) introduce a variant of tau that causes disruption of the tau-dependent signalling complex in neurons of the subject. The invention also relates to vectors, compositions and kits for treating or preventing a neurological condition mediated by a tau-dependent signalling complex in neurons of a subject.

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

Methods and small molecule compounds for inhibition of sodium channels are provided. One example of a class of compounds that may be used is represented by the compound of Formula (I) or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, R, R.sub.1, R′.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 are as described herein.

Methods and small molecule compounds for inhibition of sodium channels are provided. One example of a class of compounds that may be used is represented by the compound of Formula (I) or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, R, R.sub.1, R′.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 are as described herein.

Compounds of Formula I are described ##STR00001##
as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric diseases and disorders in a subject in need are also disclosed.