111 results about "Adrenergic agonist" patented technology

The present invention pertains to the identification of moieties and methods of using the same for preventing tolerance to bronchodilators. More specifically, the present invention pertains to the identification of compositions and methods which are capable of preventing tolerance to beta2-adrenergic agonists. The methods and compositions according to the invention are also useful as analytical tools for functional studies and as combination therapeutic tools.

A sympatholytic cardiovascular agent delivered by a drug delivery pump to a central nervous system site to alleviate symptoms and otherwise treat heart failure (HF) and pathologies associated with HF. The drug delivery pump can be external or implantable infusion pump (IIP) coupled with a drug infusion catheter extending to the site. A patient activator can command delivery of a dosage and / or an implantable heart monitor (IHM) coupled with a sensor can detect physiologic parameters associated with HF (or pathologies associated with HF) and trigger dosage delivery. The IIP and IHM can be combined into a single implantable medical device (IMD) or can constitute separate IMDs that communicate by any of known communication mechanisms. The sympatholytic cardiovascular agent is one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist, e.g., clonidine, p-aminoclonidine, guanabenz, lidamidine, tizanidine, moxonidine, methyldopa, xylazine, guanfacine, detomidine, medetomidine, and dexmedetomidine.

A method and means for delivery of drugs to the chorio-retina and the optic nerve head which comprises contacting the surface of the eye with an effective amount of drug for treatment of chorio-retina and optic nerve head and a physiologically acceptable adrenergic agent for enhancing delivery of the drug to these tissues in an ophtalmologically acceptable carrier, said adrenergic agent being selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof.

Pharmaceutical compositions comprising at least one alpha2-adrenergic agonist or baclofen and at least one alpha1-adrenergic agonist are disclosed. Pharmaceutical compositions comprising tizanidine and modafinil are disclosed. Methods for reducing somnolence, sleepiness, lethargy, dizziness, drowsiness, somnolence, tiredness, lightheadedness, increased weakness, confusion, unsteadiness, clumsiness, or a combination of the symptoms thereof in a human patient; treating pain; and attenuating muscle spasticity, using pharmaceutical compositions comprising at least one alpha2-adrenergic agonist or baclofen and at least one alpha1-adrenergic agonist are disclosed.

Methods and compositions for modulating the mobilization of stem cells, particularly for promoting or increasing the mobilization of hematopoietic stem cells from the bone marrow to the peripheral blood are disclosed. In particular, the invention relates to the use of adrenergic agonists that act in concert with a mobilization compound or agent. The mobilization agent(s) may act to decrease the expression or function of the chemokine, CXCL12, or may act to block or antagonize CXCR4. The invention also relates to methods of using these compounds or agents for enhancing the mobilization of hematopoietic stem cells when harvesting of the stem cells is necessary for the treatment of diseases, disabilities or conditions whereby transplantation of such cells would be beneficial in ameliorating the symptoms associated with such diseases, disabilities or conditions. Methods of screening for novel agents and pharmaceutical compositions comprising these agents are also disclosed.

Combinations comprising (a) a β2 agonist and (b) an antagonist of M3 muscarinic receptors which is 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, in the form of a salt having an anion X, which is a pharmaceutically acceptable anion of a mono or polyvalent acid are useful, e.g., for the treatment of respiratory disease, e.g., asthma or chronic obstructive pulmonary disease.

A method is provided for using α2δ subunit calcium channel modulators or other compounds that interact with the α2δ calcium channel subunit in combination with one or more compounds with smooth muscle modulatory effects to treat pain. According to the present invention, α2δ subunit calcium channel modulators include GABA analogs (e.g., gabapentin and pregabalin), fused bicyclic or tricyclic amino acid analogs of gabapentin, and amino acid compounds. Compounds with smooth muscle modulatory effects include antimuscarinics, β3 adrenergic agonists, spasmolytics, neurokinin receptor antagonists, bradykinin receptor antagonists, and nitric oxide donors.

A drug that inhibits NMDA receptors (such as ketamine, a surgical anesthetic) is continuously administered to patients suffering from neuropathic pain. Unless the NMDA antagonist drug has inherent safening activity, this treatment requires a “safener” drug to prevent the neurotoxic side effects of NMDA antagonists. One class of safener drugs that increase the efficacy of the treatment include alpha-2 adrenergic agonists, such as clonidine. The treatment lasts for several days and nights, continuously. A maximum tolerated dosage is titered for each patient, such as by observing slurring of speech, and the patient does not lose consciousness except during normal sleep. Magnesium and / or drugs that inhibit ketamine-degrading enzymes can also be used. Patients who suffered for years from chronic intractable pain emerged from this treatment with apparently permanent relief, or with lasting reductions in their levels of pain.

Compositions and methods for the treatment of anorectal disorders are provided in which certain combinations of NO donors, PDE inhibitors, superoxide (O2−) scavengers, β-adrenergic agonists, cAMP-dependent protein kinase activators, α1-adrenergic antagonists, L-type Ca2+ channel blockers, estrogens, ATP-sensitive K+ channel activators and smooth muscle relaxants are used.

PCT No. PCT / US97 / 15230 Sec. 371 Date May 4, 1998 Sec. 102(e) Date May 4, 1998 PCT Filed Aug. 28, 1997 PCT Pub. No. WO98 / 09625 PCT Pub. Date Mar. 12, 1998Disclosed herein are selective beta 3 adrenergic agonists represented by the following structural formula: The variables in the structural formula shown above are defined in the specification. Also disclosed are methods of using these compounds for agonizing the beta 3 adrenergic receptor in patients in need of such treatment, for example, patients in need of treatment for obesity or Type II diabetes.

The present invention discloses a novel compound and method for the treatment of inflammatory autoimmune diseases, for example, rheumatoid arthritis, using α-adrenergic antagonists and β-adrenergic agonists in combination. Treatment of animals, namely humans, with an α-adrenergic antagonist, preferably, phentolamine, and a β-adrenergic agonist, preferably terbutaline, in combination can significantly suppress the joint destruction and inflammation due to disease in these animals.

Combinations comprising (a) a β2 agonist and (b) an antagonist of M3 muscarinic receptors which is 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane, in the form of a salt having an anion X, which is a pharmaceutically acceptable anion of a mono or polyvalent acid are useful, e.g., for the treatment of respiratory disease, e.g., asthma or chronic obstructive pulmonary disease.

The present invention relates to a .beta..sub.3 adrenergic receptor agonist of formula (I) or a pharmaceutical salt thereof, which is capable of increasing lipolysis and energy expenditure in cells and, therefore, is useful for treating Type II diabetes and / or obesity. The compound can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compound can be used to reduced neurogenic inflammation or as an antidepressant agent. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for decreasing gut motility are also disclosed.

A sympatholytic cardiovascular agent delivered by a drug delivery pump to a central nervous system site to alleviate symptoms of acute or chronic cardiac insult or impaired cardiac performance. The drug delivery pump can be external or implantable infusion pump (IIP) coupled with a drug infusion catheter extending to the site. A patient activator can command delivery of a dosage and / or an implantable heart monitor (IHM) coupled with a sensor can detect physiologic parameters associated with cardiac insult or impaired cardiac performance and trigger dosage delivery. The IIP and IHM can be combined into a single implantable medical device (IMD) or can constitute separate IMDs that communicate by any of known communication mechanisms. The sympatholytic cardiovascular agent is one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist (e.g., clonidine, p-aminoclonidine, guanabenz, lidamidine, tizanidine, moxonidine, methyldopa, xylazine, guanfacine, detomidine, medetomidine, and dexmedetomidine).

Guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist and / or pterin salvage pathway tetrahydrobiopterin synthesis antagonists are administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e.g., for prophylactic or curative effect for endotoxin- or cytokine-induced hypotension or for restoration of vascular contractile sensitivity to pressor agents in the treatment of such hypotension). The tetrahydrobiopterin synthesis antagonist may be administered with alpha 1-adrenergic agonist or with nitric oxide synthase inhibitor. The tetrahydrobiopterin synthesis antagonists are also administered to attenuate inflammation caused by induced nitric oxide production in immune cells. Unwanted counterproductive or side effects can be eliminated or ameliorated by administration additionally of levodopa with or without carbidopa and L-5-hydroxytryptophane.

A method is provided for using α2δ subunit calcium channel modulators or other compounds that interact with the α2δ calcium channel subunit in combination with one or more compounds with smooth muscle modulatory effects to treat and / or alleviate the symptoms associated with painful and non-painful lower urinary tract disorders in normal and spinal cord injured patients. According to the present invention, α2δ subunit calcium channel modulators include GABA analogs, e.g., gabapentin and pregabalin, fused bicyclic or tricyclic amino acid analogs of gabapentin, and amino acid compounds. Compounds with smooth muscle modulatory effects include antimuscarinics, β3 adrenergic agonists, spasmolytics, neurokinin receptor antagonists, bradykinin receptor antagonists, and nitric oxide donors.

Disclosed is an extended release pharmaceutical formulation containing at least an alpha-2 adrenergic agonist, such as tizanidine, for the treatment and prevention of spasticity in a subject, e.g., painful inflammatory conditions associated with skeletal muscle spasms.

The present invention is in the field of medicine, particularly in the treatment of Type II diabetes and obesity. More specifically, the present invention relates to selective beta3 adrenergic receptor agonists useful in the treatment of Type II diabetes and obesity. The invention provides compounds and method of treating type II diabetes, comprising administering to a mammal in need thereof compounds of the Formulas I and II:

A method is provided for using α2δ subunit calcium channel modulators or other compounds that interact with the α2δ calcium channel subunit in combination with one or more compounds with smooth muscle modulatory effects to treat and / or alleviate the symptoms associated with painful and non-painful lower urinary tract disorders in normal and spinal cord injured patients. According to the present invention, α2δ subunit calcium channel modulators include GABA analogs (e.g. gabapentin and pregabalin), fused bicyclic or tricyclic amino acid analogs of gabapentin, and amino acid compounds. Compounds with smooth muscle modulatory effects include antimuscarinics, β3 adrenergic agonists, spasmolytics, neurokinin receptor antagonists, bradykinin receptor antagonists, and nitric oxide donors.

A medical device, comprising: an array of microneedles, and a coating disposed on the microneedles, wherein the coating comprises: a local anesthetic selected from the group consisting of lidocaine, prilocaine, and a combination thereof; and a local anesthetic dose-extending component selected from the group consisting of alpha 1 adrenergic agonists, alpha 2 adrenergic agonists, and a combination thereof; wherein the local anesthetic is present in an amount of at least 1 wt-% based upon total weight of solids in the coating, and wherein the dose-extending component / local anesthetic weight ratio is at least 0.0001; a medical device, comprising an array of dissolvable microneedles, the microneedles comprising: a dissolvable matrix material; at least 1 wt-% of a local anesthetic selected from the group consisting of lidocaine, prilocaine, and a combination thereof; and a local anesthetic dose-extending component selected from the group consisting of alpha 1 adrenergic agonists, alpha 2 adrenergic agonists, and a combination thereof; wherein the dose-extending component / local anesthetic weight ratio is at least 0.0001, and wherein wt-% is based upon total weight of solids in all portions of the dissolvable microneedles which contain the local anesthetic; a method of extending a topically delivered local anesthetic dose in mammalian tissue using the devices; and methods of making the devices are provided.

An ophthalmic formulation having an effective amount of a parasympathomimetic agent comprising pilocarpine, or a pharmaceutically acceptable salt thereof, and one or more α1 adrenergic agonists or antagonists is disclosed. The ophthalmic formulation may enable treatment of conditions adversely affecting the visual acuity of a patient, including presbyopia. A method of using the disclosed ophthalmic formulation to treat or ameliorate symptoms of presbyopia is also disclosed.

Compounds of Formula 1 where the variables have the meaning defined in the specification are agonists of alpha2 adrenergic receptors. Several compounds of the disclosure are specific or selective to alpha2B and / or alpha2C adrenergic receptors in preference over alpha2A adrenergic receptors. Additionally some of the claimed compounds have no or only minimal cardivascular and / or sedatory activity. The compounds of Formula 1 are useful as medicaments in mammals, including humans, for treatment of diseases and or alleviations of conditions which are responsive to treatment by agonists of alpha2 adrenergic receptors. Compounds of Formula 1 which have no significant cardiovascular and / or sedatory activity are useful for treating pain and other conditions with minimal side effects.

Methods for treating or preventing cardiomyopathy in a subject by administering an al adrenergic receptor agonist, wherein the treatment does not result in increased blood pressure are provided.

Compositions and methods for preventing and treating wasting disorders, such as cachexia and anorexia, are provided. In one aspect, the present invention provides a method for preventing and treating a wasting disorder in a mammal. In one embodiment, the method of the invention comprises administering to such mammal a macrolide and a β2-adrenergic agonist in combination such that the macrolide and said β2-agonist are administered in amounts effective to prevent or at least alleviate said wasting disorder.

Methods and compositions for modulating the mobilization of stem cells, particularly for promoting or increasing the mobilization of hematopoietic stem cells from the bone marrow to the peripheral blood are disclosed. In particular, the invention relates to the use of adrenergic agonists that act in concert with a mobilization compound or agent. The mobilization agent(s) may act to decrease the expression or function of the chemokine, CXCL12, or may act to block or antagonize CXCR4. The invention also relates to methods of using these compounds or agents for enhancing the mobilization of hematopoietic stem cells when harvesting of the stem cells is necessary for the treatment of diseases, disabilities or conditions whereby transplantation of such cells would be beneficial in ameliorating the symptoms associated with such diseases, disabilities or conditions. Methods of screening for novel agents and pharmaceutical compositions comprising these agents are also disclosed.

Compounds of Formula 1 where the variables have the meaning defined in the specification are agonists of alpha2 adrenergic receptors. Several compounds of the disclosure are specific or selective to alpha2B and / or alpha2C adrenergic receptors in preference over alpha2A adrenergic receptors. Additionally some of the claimed compounds have no or only minimal cardivascular and / or sedatory activity. The compounds of Formula 1 are useful as medicaments in mammals, including humans, for treatment of diseases and or alleviations of conditions which are responsive to treatment by agonists of alpha2 adrenergic receptors. Compounds of Formula 1 which have no significant cardiovascular and / or sedatory activity are useful for treating pain and other conditions with minimal side effects.

Method and apparatus are disclosed for applying a therapeutic amount of a non-systemic vasoconstrictor inside the uterus to control abnormal uterine bleeding. The abnormal bleeding can be due to excessive menstrual blood flow, bleeding from a surgical procedure, postpartum bleeding or any other acute or chronic condition. The vasoconstrictor includes topical agents such as an alpha-adrenergic agonist, for example oxymetazoline. The delivery system can include a catheter having means for retaining position of a distal portion within the uterus. A proximal portion can extend outside of the body for coupling to a vasoconstrictor source, or alternatively, the proximal portion can terminate within the vaginal canal and include a docking port for coupling to a source of vasoconstrictor that is inserted therein. In other embodiments, an applicator is disclosed that is positioned in fluid communication with the lumen of the cervix and allows application of a vasoconstrictor therein.

The invention discloses a potentiometric sensing electrode for testing an adrenergic agonist and a sensor thereof. The sensing electrode comprises an electrode cable, a platinum electrode, an insulating sleeve, an electrode cap, a molecular imprinting membrane and a potential electrode solution; the platinum electrode is arranged in the insulating sleeve, and the electrode cable is drawn out from the upper end portion of the insulating sleeve; an end cap of the electrode cap is in an annular hollow structure, and an inner circle area on the inner side of the end cap is covered with the molecular imprinting membrane provided with a molecular imprinting pore structure; the outer side on the lower end portion of the insulating sleeve is closely sleeved with the electrode cap to fix the molecular imprinting membrane between the electrode cap and the insulating sleeve; and the potential electrode solution immersing at least the lower end of the platinum electrode is poured in the insulating sleeve. According to the potentiometric sensing electrode for detecting the adrenergic agonist and the sensor thereof, the potentiometric sensing electrode uses the molecular imprinting membrane with high peculiarity as a receptor of an electrochemical sensor and has the advantages that the test sensitivity is high, the operation is simple, the sensing electrode is convenient to carry, and the like, and field tests of adrenergic agonists are achieved.