95 results about "Adrenergic receptor antagonists" patented technology

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

It has been discovered that the stimulation of beta -adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta -adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta -adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta -adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

Compositions, and methods of use thereof, are provided for the prevention or treatment of side effects associated with the use of drugs that act as 5HT2 / 5HT3 serotonin receptor antagonists and alpha-2 adrenergic receptor antagonists (5HT2 / 5HT3 antagonist / alpha-2 antagonist). The method involves using dopamine-releasing compounds, such as amantadine, anticonvulsants, such as zonisamide, or dopamine / norepinephrine reuptake inhibitors, such as bupropion, in combination with 5HT2 / 5HT3 antagonist / alpha-2 antagonists, such as mirtazapine, to reduce the excessive daytime drowsiness and / or weight gain associated with 5HT2 / 5HT3 antagonist / alpha-2 antagonist use for the treatment of disorders, such as, depression, schizophrenia, anxiety disorders, sleep-related breathing disorders, insomnia, migraine headache, chronic tension-type headache, hot flashes, lower back pain, neuropathic pain and functional somatic syndromes. Formulations of dopamine-releasing compounds or anticonvulsants with 5HT2 / 5HT3 antagonist / alpha-2 antagonists are provided. In particular embodiments, combination therapy with mirtazapine and zonisamide provides relief from chronic low back pain, while reducing or avoiding side effects associated with monotherapy with mirtazapine or zonisamide.

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

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.

Combination therapies of an alpha-2 adrenergic receptor agonist and an alpha-2 adrenergic receptor antagonist at a concentration effective to potentiate but not antagonize a therapeutic effect of the alpha-2 adrenergic receptor agonist are provided. Also provided are methods for use of these combination therapies in potentiating the therapeutic effects of alpha-2 adrenergic receptor agonists, inhibiting development of acute and / or chronic tolerance to alpha-2 adrenergic receptor agonists and treating conditions treatable by alpha-2 adrenergic receptor agonist therapy in a subject. In addition, a method for reversing alpha-2 adrenergic receptor agonist tolerance and / or restoring therapeutic effect of an alpha-2 adrenergic receptor agonist in a subject via administration of an alpha-2 adrenergic receptor antagonist at a concentration effective to potentiate, but not antagonize, the therapeutic effect of the alpha-2 adrenergic receptor agonist is provided.

The disclosure provides a composition for controlling pupil dilation comprising about 0.001% to about 1.0% by weight of an alpha-adrenergic receptor antagonist selected from phentolamine, phentolamine mesylate, or a phentolamine salt; and at least one excipient selected from the group consisting of a buffer, tonicity agent, preservative, antioxidant, surfactant, solubilizer, cosolvent, and a combination thereof. A method of controlling pupil dilation in a subject in need thereof, comprising administering a therapeutically effective amount of the composition is also provided.

The present invention describes novel nitrosated and / or nitrosylated α-adrenergic receptor antagonists, and novel compositions containing at least one nitrosated and / or nitrosylated α-adrenergic receptor antagonist, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or are a substrate for nitric oxide synthase, and / or one or more vasoactive agents. The present invention also provides novel compositions containing at least one α-adrenergic receptor antagonist, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and / or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, neurodegenerative disorders, vasospastic diseases, cognitive disorders, urge incontinence, or overactive bladder, and for reversing the state of anesthesia.

The present invention provides compositions and stable liquid formulations comprising alpha adrenergic receptor antagonists and use thereof for increasing blood flow. In one embodiment, the stable liquid formulations of this invention are useful for reversing the effects of an anesthetic agent, preferably a long-lasting local anesthetic agent administered in conjunction with an alpha adrenergic receptor agonist. The invention further relates to drug delivery systems for administering alpha adrenergic receptor antagonists.

A safe and effective treatment for glaucoma for mammalian species comprises the steps of applying insulin and / or insulin like growth factors (IGF-1) to an eye. In addition to the insulin, another therapeutic agent may be applied to enhance the activity of the insulin. The therapeutic agent may be a pharmaceutical agent or a biochemical pharmaceutical agent. The therapeutic agents include prostaglandin analogs, topical beta-adrenergic receptor antagonists-β blockers, Alpha2-adrenergic agonists hair growth therapeutic agents, beta2-agonist action agents, parasympathomimetic miotic agents, carbonic anhydrase inhibitors, and Physostigmine. In another embodiment, a combination of at least two agents are applied to the eye. To enhance the effect of the insulin, uptake facilitators may be used. Additionally, an antibacterial agent may be applied to control bacterial infection.

The invention describes novel nitrosated and / or nitrosylated compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and / or nitrosylated compound, and, optionally, at least one nitric oxide donor and / or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one compound of the invention, that is optionally nitrosated and / or nitrosylated, and, optionally, at least one nitric oxide donor compound and / or at least one therapeutic agent. The invention also provides methods for treating ophthalmic disorders. The nitrosated and / or nitrosylated compounds are preferably nitrosated and / or nitrosylated (3-adrenergic antagonists and nitrosated and / or nitrosylated angiotensin-converting enzyme (ACE) inhibitors.

The invention is directed to nitrosated or nitrosylated alpha-adrenergic receptor antagonists, compositions comprising alpha-adrenergic receptor antagonists that are optionally substituted with at least one NO or NO2 moiety and compounds that donate, transfer or release nitric oxide or elevate levels of endogenous endothelium-derived relaxing factor, and methods for treating sexual dysfunctions in males and females. The invention also provides methods for treating female sexual dysfunctions by administering S-nitrosothiol compounds.

The present invention relates to a method for inhibiting fibrogenesis, especially liver fibrogenesis, which method comprises administering an effective amount of an adrenergic receptor antagonist to a patient in need of such treatment.

The present invention provides compositions and stable liquid formulations comprising alpha adrenergic receptor antagonists and use thereof for increasing blood flow. In one embodiment, the stable liquid formulations of this invention are useful for reversing the effects of an anesthetic agent, preferably a long-lasting local anesthetic agent administered in conjunction with an alpha adrenergic receptor agonist.

The disclosure provides a pharmaceutical composition for treating social anxiety, performance anxiety, and social phobia comprising a therapeutic amount for die treatment of a patient of a β-adrenergic receptor antagonist, an anti-diarrheal compound, and an optional anticholinergic compound. The β-adrenergic receptor antagonist may be the lipophilic β-blocker propranolol HCl, the anti-diarrheal compound may be the opioid diphenoxylate HCl, and the optional anticholinergic compound may be atropine sulfate. The composition for treating performance anxiety and social phobia can further include a pharmaceutically acceptable carrier. A method of preventing or treating social anxiety, performance anxiety, and social phobia in a patient is also provided, comprising administering a composition of the disclosure to a patient in need of such treatment. The composition administered in the present method comprises a therapeutic amount of a β-adrenergic receptor antagonist, an anti-diarrheal compound, and an optional anticholinergic compound.

The invention provides methods for (a) prolonging time to hospitalization for heart failure; (b) prolonging time to first hospitalization for heart failure; (c) reducing the total number of days a patient with heart failure spends in the hospital for heart failure for a single hospital stay (i.e., reducing the duration of a single hospital stay for a patient with heart failure); (d) reducing the total number of days a patient spends in the hospital for heart failure for multiple hospital stays (i.e., two or more hospital stays); (e) reducing the number of hospital admissions for heart failure; (f) reducing mortality and reducing hospitalizations for heart failure (e.g., the total number of days in the hospital and / or the number of hospital visits); (g) increasing the left ventricular ejection fraction in a heart failure patient; (h) treating a sexual dysfunction (e.g., erectile dysfunction and female sexual dysfunction) (j) treating a headache in a heart failure patient by administering a non-steroidal antiinflammatory compound (i.e., NSAIDs); (k) treating a heart failure patient who has a history of hypertension (but who is not currently diagnosed with hypertension); (l) improving the quality of life in a heart failure patient based on the Minnesota Living with heart failure questionnaire; (m) decreasing the levels of B-type natriuretic peptide; (n) treating hypertension in a heart failure patient; (o) lowering blood pressure in a heart failure patient; (p) treating labile hypertension; (q) treating idiopathic hypertension; (r) increasing patient compliance with medication dosing in a heart failure patient; (s) treating hypertension in a patient with a dilated heart; (t) treating ischemic disease and / or coronary artery disease; and (u) reducing cardiomegaly in a patient in need thereof comprising administering to the patient a therapeutically effective amount of (i) a hydralazine compound or pharmaceutically acceptable salt thereof, (ii) isosorbide dinitrate and / or isosorbide mononitrate, and (iii) optionally at least one compound selected from the group consisting of angiotensin converting enzyme inhibitors, β-adrenergic antagonists, angiotensin II antagonists, aldosterone antagonists, cardiac glucosides (digitalis), and diuretic compounds.

The invention provides a group of novel medicinal compositions for treating infectious diseases of the urogenital system such as urinary tract infection and prostatitis, wherein the composition comprises the pharmaceutical effective combinations of the following materials: I) anti-infectious medicaments and second compounds of the precursors and pharmaceutically acceptable salts of the anti-infectious medicaments; II) medicaments for treating urethra stimulative symptoms, such as muscarinic receptor antagonist, alpha-adrenergic receptor antagonist and 5-alpha-reductase inhibitor or phosphodiesterase (PDE) antagonist and second compounds of the precursors and pharmaceutically acceptable salts of the medicaments; and III) analgesic medicaments or dopes and second compounds of the precursorsand pharmaceutically acceptable salts of the analgesic medicaments or dopes. The three classes of medicaments can be combined two by two (such as I+II, II+III or I+III) or combined together (such as I+II+III). The invention also provides group of novel methods for treating infectious diseases of the urogenital system such as urinary tract infection and prostatitis, which comprises a step of usinga therapeutically effective dose of the compositions of the invention.

The combined use of (R)-5-(2-{[2-(2-ethoxyphenoxy)ethyl]amino}propyl)-2-methoxybenzene-1-sulfonamide (tamsulosin), or its pharmaceutically acceptable salt, and (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid (3R)-quinuclidin-3-yl ester (solifenacin), or its pharmaceutically acceptable salt, for the preparation Of a medicament for the improvement of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS / BPH) with a substantial storage component is provided.

The invention relates to the field of urogenital system and lower urinary tract diseases. The invention provides a new medicinal composition. The composition comprises medicinal effective compositionof the following substances: I) a first compound selected from medicaments for treating bladder hyperactivity such as muscarinic receptor antagonist and medicaments for treating prostate hyperplasia such as 5alpha-reductase inhibitor and alpha-adrenergic receptor antagonist, precursors thereof and pharmacologically acceptable salts thereof, II) a second compound selected from PDE-5 enzyme antagonist, precursor thereof and pharmacologically acceptable salt thereof, and III) a second compound selected from antidiuretic, precursor thereof and pharmacologically acceptable salt thereof, and optional pharmacologically acceptable vector thereof or diluent. The three medicaments can be combined two by two (such as I + II, or I + III, or II + III), or combined together at the same time (such as I +II + III). The invention also provides a group of methods for treating urogenital system and lower urinary tract diseases of mammals comprising people, wherein the methods comprise applying treatmenteffective dose of the composition to the mammals comprising people needing the treatment.

The present invention is focused primarily toward pro re nata (“as needed”) treatments for a psychiatric condition or disorder or the symptoms thereof, including the symptoms of acute anxiety and panic in living animals, including humans. The present invention encompasses pharmaceutical compositions as combination therapies containing at least one beta adrenergic receptor antagonist and at least one muscarinic receptor antagonist. The invention provides methods for treating psychiatric condition or disorder or the symptoms thereof, including acute anxiety and panic comprising administering a pharmaceutical composition consisting essentially of a beta adrenergic receptor antagonist drug and an antiemetic muscarinic receptor antagonist drug in a therapeutically effective amount to stop or reduce the symptoms of anxiety and / or panic. The pharmaceutical compositions are administered as treatments immediately in advance of, at the onset of, or during an acute anxiety and / or panic episode.

Compounds which are alpha-1A / B adrenoceptor antagonists and which are represented by Formula I: wherein Q is a monocyclic or bicyclic optionally-substituted heterocyclic ring as defined herein; Z is —C(═O)— or —S(═O)2—; R and R′ are lower alkyl; R5 is halogen, cyano, hydroxy, —R6, or —OR6; and R6 is alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclo, or substituted heterocyclo; and pharmaceutically-acceptable salts, hydrates, prodrugs, and isomers thereof.

The invention discloses a medicinal composition, which comprises two or three of a, b and c, wherein a is long-chain fatty acid compounds of a formula I or plant extract containing the same; b is flavonoid compounds of a formula II or plant extract containing the same; and c is the following alkaloid compounds or plant extract containing the same: N1,N5,N10-tri-(E / Z)-coumaroyl spermidine, 1-O-(beta-D-glucose)-(2S, 3S, 4R)-2N-[(2'R)-2'-hydroxytetracosenoicacid]-octadecylene-3,4-diol, putrescine and indol-3-acetic acid. The medicinal composition of the invention can be used for preparing aromatizing enzyme inhibitor, 5alpha reductase inhibitor, alpha1-adrenergic receptor antagonist, cyclooxygenase-2 inhibitor, prostate-specific antigen (PSA) secretion inhibitor, anti-inflammation medicamentor medicament for resisting prostatic hyperplasia, prostatitis or prostatic cancer.

Methods of reversing local anesthesia are disclosed. The methods comprise administering a local anesthetic and alpha adrenergic receptor agonist to induce local anesthesia followed by reversing anesthesia with a low dose of an alpha adrenergic receptor antagonist. Also disclosed are kits comprising a local anesthetic, an alpha adrenergic receptor agonist and a low dose of an alpha adrenergic receptor antagonist.

The instant invention relates to compositions and methods for treating or preventing bone diseases. In certain aspects, the invention provides compositions comprising a β-adrenergic antagonist or agonist associated to a bone-targeted molecule, as well as methods of modulating bone mass and / or growth in a mammal by administering a composition of the present invention. In other aspects, the invention provides methods of modulating bone mass and / or growth in a mammal by administering a composition comprising a β2-selective antagonist or agonist.

The invention relates to the field of cosmetics, and provides a skin care product for skin whitening and a preparation method thereof. The skin care product for skin whitening provided by the invention comprises oil-phase raw materials, water-phase raw materials and third-phase raw materials, wherein the oil-phase raw materials comprise an emulsifying agent, an emollient and succinate dimethoxy-methyl-nor-aporphine; the water-phase raw materials comprise a skin humectant, a metal chelating agent and reverse osmosis water; and the third-phase raw materials comprise a preservative and perfume. The calcium current principle is adopted to impede the activation of tyrosinase for the skin care product for skin whitening and preparation method thereof provided by the invention, thus the effects of skin whitening and color spot fading are achieved. The skin care product for skin whitening provided by the invention is added with nor-aporphine derivatives, thus the skin care product can interfere the inflow and outflow of the calcium current in cells; and the activation of protein kinase C is inhibited by an adrenergic antagonist which locks the calcium exchange, thereby impeding the activation of tyrosinase, achieving the effects of skin whitening and color spot fading.