40 results about "Voltage-gated calcium channel (VGCC)" patented technology

The described invention provides a method for reducing visual loss and for treating one or more of adverse consequence of an eye disease, including abnormal intraocular pressure, retinal vascular disease, retinal ganglion cell death, or a combination thereof in order to reduce visual loss. The method entails providing a flowable particulate composition that contains a particulate formulation comprising a plurality of particles of uniform size distribution, a therapeutic amount of a therapeutic agent selected from a voltage-gated calcium channel antagonist, an endothelin receptor antagonist, or a combination thereof, and optionally an additional therapeutic agent, wherein the particles are of uniform size distribution, and wherein each particle comprises a matrix; and a pharmaceutically acceptable carrier. The pharmaceutical composition is characterized by: dispersal of the therapeutic agent throughout each particle, adsorption of the therapeutic agent onto the particles, or placement of the therapeutic agent in a core surrounded by a coating, sustained release of the therapeutic agent and optionally the additional therapeutic agent from the composition, and a local therapeutic effect that is effective to reduce signs or symptoms of the adverse consequence without entering systemic circulation in an amount to cause unwanted side effects. The method further entails administering a therapeutic amount of the pharmaceutical composition by a means for administration at a site of administration. The administering includes topically, parenterally, or by implantation. Sites of administration include intraocularly, intraorbitally, or into subconjunctival space.

Disclosed are mammalian nucleic acid sequences encoding α1I subunit isoforms of a voltage-gated calcium channel. Specifically disclosed are novel variants of the α1I subunit designated herein as α1I-1 and α1I-2. In other aspects, the disclosure relates to expression vectors which encode the novel subunits of the invention, as well as cells containing such vectors. Antibodies specific for each of the variant subunits are also provided. The nucleic acid sequences of the invention find application, for example, in screening for compounds which modulate the activity of voltage-gated calcium channels and also in diagnostic methods for diagnosing various T-type channel mediated disorders, e.g., epilepsy, cancer, pain, sleep disorders and the autoimmune disease Lambert-Eaton Syndrome. Diagnosing defects in α1I subunit genes of a patient with a neuronal disease such as epilepsy are also included. An additional application of the nucleic acid sequences of the invention is in therapeutic methods of treatment for α1I subunit mediated disorders.

The present invention relates to new compounds of formula (I): showing great affinity and activity towards the subunit [alpha]2[delta] of voltage-gated calcium channels (VGCC), especially the [alpha]2[delta]-1subunit of voltage-gated calcium channels or dual activity towards subunit [alpha]2[delta] of voltage-gated calcium channels (VGCC), especially the [alpha]2[delta]-1subunit of voltage-gated calcium channels, and the noradrenaline transporter (NET).

The described invention provides site-specific sustained release microparticulate formulations containing a therapeutic amount of an L-type voltage gated calcium channel inhibitor, a PLGA polymer comprising from 25% to 50% glycolide, and a hyaluronic acid. A therapeutic amount of the formulation is effective to reduce signs or symptoms of delayed cerebral ischemia comprising one or more of a cortical spreading ischemia, a cortical spreading depolarization, a plurality of microthromboemboli, or an angiographic vasospasm after brain injury in a mammal, while reducing the risk of systemic hypotension, cardiac dysfunction, anoxia, and intracranial hypertension.

The described invention provides a method for reducing visual loss and for treating one or more of adverse consequence of an eye disease, including abnormal intraocular pressure, retinal vascular disease, retinal ganglion cell death, or a combination thereof in order to reduce visual loss. The method entails providing a flowable particulate composition that contains a particulate formulation comprising a plurality of particles of uniform size distribution, a therapeutic amount of a therapeutic agent selected from a voltage-gated calcium channel antagonist, an endothelin receptor antagonist, ora combination thereof, and optionally an additional therapeutic agent, wherein the particles are of uniform size distribution, and wherein each particle comprises a matrix; and a pharmaceutically acceptable carrier.

The present invention relates to new compounds of formula (I):showing great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels or dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels, and the noradrenaline transporter (NET).

The present invention relates to new compounds of formula (I):showing great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels or dual activity towards subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels, and the noradrenaline transporter (NET).

The present invention relates to homopiperazinyl and homopiperidinyl quinazoline-4 (3H)-one derivatives having dual pharmacological activity on both the alpha2delta subunit of the voltage-gated calcium channel and the Scima-1 (sigma1) receptor, to processes for the preparation of such compounds, to pharmaceutical compositions comprising the same, and to pharmaceutical compositions comprising the same. And to the use thereof in therapy, in particular for the treatment of pain.

The present invention relates to ortho substituted phenylpyrazolo- and pyrrolo-pyridazine derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to substituted pyrrolidinyl and piperidinyl pyrazolopyridazine derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ−1 subunit, of the voltage-gated calcium channel and the Noradrenaline transporter (NET), to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The Voltage-Gated Calcium Channel auxiliary subunit α2δ-1 is the target / receptor of gabapentinoid compounds known to exert therapeutic effects as for example in Epilepsy and Neuropathic pain. Gabapentinoids are known to exert their action via binding Arginine (R) within an RRR motif located at the N-terminal of the α2δ-1. The present invention describes a novel binding site for gabapentinoids which is located within the VGCC_a2 domain and within an IKAK aminoacid sequence of the α2δ-1. Such newly identified amino acid binding site finds utility in the identification and characterization of novel compounds with therapeutic properties in Neuropathic Pain and in other disorders and conditions in which α2δ-1 is involved in.

The present invention relates to a novel gene encoding a protein termed voltage gated calcium channels β subunit anchoring regulator protein (VDCC BARP) or a peptide fragments thereof. The present invention also relates to the use of VDCC BARP in Modulation of voltage gated calcium channels via altering the concentration of VDCC BARP or a peptide fragments thereof.

The present invention relates to piperazinyl and piperidinyl quinazolin-4(3H)-one derivatives having pharmacological activity towards the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel, in particular having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor. The present invention also relates to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to new compounds of formula (I) that show great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels or dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels, and the noradrenaline transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to arylamide derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to new compounds of general formula (I) that show dual activity towards α2δ subunit of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit, and to the noradrenallne transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to new compounds of general formula (I) showing great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels or dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels, and the μ-opioid receptor (MOR or mu-opioid receptor). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to new compounds of formula (I) that show great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), or dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC) and the noradrenaline transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to new compounds of general formula (I) that show great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially α2δ-1 subunit of voltage-gated calcium channels or dual activity towards subunit α2δ of voltage-gated calcium channels (VGCC), especially α2δ-1 subunit of voltage-gated calcium channels, and noradrenaline transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to pyrazole derivatives having pharmacological activity towards the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel, in particular having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor. The present invention also relates to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention provides systems, compositions and methods for treatment of dopaminergic disorders (e.g., Parkinson's disease) using the combination of a first compound that inhibits a voltage-gated calcium channel of the type Cav1.3 (e.g., a dihydropyridine such as isradipine), and a second compound that is monoamine oxidase inhibitor and / or is a nitric oxide synthase inhibitor (e.g., rasagiline or derivative thereof).

The present invention relates to new compounds of general formula (I) that show dual activity towards alpha 2 delta subunit of voltage-gated calcium channels (VGCC), especially the alpha 2 delta-1 subunit, and to the noradrenaline transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to (hetero)arylalkylamino-pyrazolopyridazine derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the Noradrenaline transporter (NET), to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to meta substituted phenylpyrazolo- and phenylpyrrolo-pyridazine derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the NET receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to new compounds of general formula (I) that show great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially α2δ-1 subunit of voltage-gated calcium channels or dual activity towards subunit α2δ of voltage-gated calcium channels (VGCC), especially α2δ-1 subunit of voltage-gated calcium channels, and noradrenaline transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to 2-phenyl-2H-pyrazolo[3,4-d]pyridazine derivatives having pharmacological activity towards the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel, in particular having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor. The present invention also relates to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to new compounds of formula (I) that show great affinity and activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), or dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC) and the noradrenaline transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.

The present invention relates to ortho substituted phenylpyrazolo- and pyrrolo-pyridazine derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to new compounds of formula (I) that show dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels, and the noradrenaline transporter (NET). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments.