Abstract: The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity, particularly involved in hypersensitive cough or itching.

Abstract: The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity, particularly involved in hypersensitive cough or itching.

Abstract: The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity particularly involved in the development and maintenance of persistent or chronic pain, and/or neurological disorders. These novel compounds are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which these ion channels are involved. The invention is also directed towards pharmaceutical formulations comprising these compounds and the uses of these compounds.

Abstract: The present invention provides compositions, and methods for local administration of certain peptides or combination with certain small molecules that produce analgesia and anti-inflammation in a mammal. Exemplary polypeptides provide peripheral analgesia and anti-inflammation when administered via local topical, subcutaneous, intradermal, or intranasal administration, to provide analgesia and anti-inflammation. Through antagonism of peripheral CGRP receptors alone, or in combination with inhibition of sensory sodium channels or anti-inflammation, the compositions of the invention provide local therapeutic pain relief with minimal undesired systemic side effects in a subject. Also provided are improved peptide delivery techniques including microneedle unit dose administering apparatus and methods.

Abstract: The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity particularly involved in the development and maintenance of persistent or chronic pain, and/or neurological disorders. These novel compounds are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which these ion channels are involved. The invention is also directed towards pharmaceutical formulations comprising these compounds and the uses of these compounds.

Abstract: Tricyclic pyrone compounds having high oral bioavailability, excellent blood-brain barrier permeability, and low toxicity are presented. Administration of the compounds to Alzheimer's Disease transgenic models resulted in substantially reduced soluble and insoluble A? species in the brain without affecting general behavior and motor coordination. Furthermore, in addition to blocking the toxicity and formation of both intraneuronal and extracellular A? aggregates, the compounds also increase cellular cholesterol efflux, restore axonal trafficking, and enhance hippocampal synaptic plasticity.