96 results about "Adrenergic receptor" patented technology

Disclosed is a needle-free applicator that is suitable for administering a solid, amorphous, mono-particulate powder composition into a body cavity of a human patient, which cavity includes a mucosal surface, wherein the applicator comprises:(i) an opaque reservoir comprising said powder composition;(ii) an optional actuating means for generating a force upon actuation of the device by a user; and(iii)a dispensing means through which, following said actuation, said powder composition may be dispensed,wherein said powder composition comprises a pharmacologically-effective dosage amount of an adrenergic receptor modulator, or a pharmaceutically-acceptable salt thereof, encapsulated in an amorphous state along with a pharmaceutically-acceptable carrier material; andwhich powder composition is less than about 4% chemically degraded after storage for:(a) at least about 3 months at 40° C. and 75% relative humidity; and / or(b) at least about 18 months at below about 30° C.; and / or(c) at least about 18 hours at above about 1 million lux of UV light.

Disclosed is a pharmaceutically-acceptable composition in the form of a solid, amorphous, mono-particulate powder comprising a mixture of:a pharmacologically-effective dosage amount of an adrenergic receptor modulator, or a pharmaceutically-acceptable salt thereof; anda pharmaceutically-acceptable carrier material, which carrier material comprises a maltodextrin with a dextrose equivalent (DE) that is above 15.Compositions are suitable for transmucosal drug delivery, including nasal delivery, by which said compositions may be loaded into a single-use nasal applicator. Compositions are preferably made by way of spray drying and may further include a disaccharide, such as lactose or trehalose which, along with the active ingredient and maltodextrin, may be spray-dried together in combination. Compositions may further comprise one or more alkyl saccharides. Preferred alkyl saccharides include sucrose esters, such as sucrose monolaurate. Preferred adrenergic receptor modulators include epinephrine (adrenaline). The compositions are thus particularly useful in the treatment of allergic reactions, including anaphylaxis.

Intranasal dry powder epinephrine compositions are described herein. The compositions include epinephrine or a pharmaceutically acceptable salt thereof, as well as a stabilizing agent and a carrier. The stabilizing agent is operable to include citric acid, or a pharmaceutically acceptable salt derived therefrom. Such intranasal compositions as described herein are useful in the treatment of health conditions which threaten the central nervous system (CNS) and impede the actions of alpha and beta-adrenergic receptors. Such health conditions include anaphylaxis, bronchospasms, respiratory impairment, organophosphate poisoning, and major adverse cardiac events (MACE).

The invention belongs to the field of medicinal chemistry, and particularly discloses a benzimidazole amine derivative, a preparation method thereof and application of the benzimidazole amine derivative as a beta2-adrenergic receptor allosteric antagonist. According to the benzimidazole amine derivative disclosed by the invention, R1 is a hydrogen atom or a bromine atom; r2 is substituted benzoyl, substituted benzyl and the like. Pharmacological results show that the benzimidazole amine derivative disclosed by the invention has relatively good antagonistic activity on beta2AR, and the functional activity of isoprenaline (ISO) can be subjected to negative allosteric regulation.

This invention relates to methods and compositions directed to mobilizing a cell in a subject by blocking CXCR4, a beta-adrenergic receptor, a GPCR, or any combination thereof. In some embodiments, the cell is a hematopoietic stem cell. In some embodiments, the method further comprises administration of G-CSF. This invention also relates to methods of treatment, methods for qualifying a subject for treatment, and methods for preparing a subject for treatment, by blocking CXCR4, a beta-adrenergic receptor, a GPCR, or any combination thereof. In some embodiments, the cell is a hematopoietic stem cell. In some embodiments, the treatment is for cancer. In some embodiments, the CXCR4 is GPC-100. In some embodiments, the method further comprises administration of G-CSF.

The invention belongs to the field of medicinal chemistry, and relates to an indole acrylic acid amide derivative as well as a preparation method and application thereof. Functional activity screening of G protein dependent signaling pathways is carried out on all synthesized compounds, and it is found that the new derivatives can be used as allosteric antagonism regulators of beta2-adrenergic receptors. Trans-indole acrylic acid with different substituent groups is used as a raw material, amide coupling is performed to obtain the novel indole acrylic acid amide derivative, and R1 is a hydrogen atom, a halogen atom, a methyl group or a methoxyl group; r2 is any one of phenyl, m-bromophenyl, m-chlorphenyl, m-fluorophenyl, m-cyanophenyl, m-methoxyphenyl, cyclohexyl and piperidyl. A biological activity test result shows that the indole acrylic acid amide derivative disclosed by the invention has relatively good antagonistic activity on beta2AR and can be used for carrying out negative allosteric regulation on the functional activity of isoproterenol.

The present application relates to novel substituted heterocyclic carboxamides, to processes for their preparation, to their use alone or in combinations for the treatment and / or prevention of diseases and to their use for producing medicaments for the treatment and / or prevention of diseases, in particular for the treatment and / or prevention of breathing difficulties including sleep-induced breathing difficulties such as central and obstructive sleep apnoea, snoring (primary and obstructive snoring), dysphagia, peripheral and cardiac vascular disorders including diabetic microangiopathies and disorders of the peripheral and central nervous system including neurodegenerative and neuroinflammatory disorders.

The present invention relates to methods of treating heart failure by administering certain compounds that modulate the activity of the beta-3 adrenergic receptor.

Described herein are methods for the identification and detection of genetic factors in the molecular pathways associated with vascular retinopathies or retinal diseases, for example mild, moderate or severe retinopathy of prematurity (ROP). Included herewith are methods of detecting genetic mutations associated with severe retinopathies, including factors in ADRβ2 pathways, which include RAPGEF3, ADCY7, ADCY9, PRKARIA, and ADCY4 variants. Further, this disclosure provides for methods of treating a subject having a detected genetic factor indicative of ROP.

The invention belongs to the field of medicinal chemistry, and relates to an indole allylamine amide derivative as well as a preparation method and application thereof. Functional activity screening of G protein dependent signaling pathways is carried out on all the synthesized compounds, and it is found that the new derivatives can be used for preparing beta2-adrenergic receptor allosteric antagonism regulator drugs. Trans-indole allylamine is used as a raw material, amide coupling is performed to obtain the novel indole allylamine amide derivative, and R1 is any one of phenyl, m-methylbenzene, m-methoxyphenyl, m-bromophenyl, m-chlorphenyl, m-fluorophenyl, o-methoxyphenyl, p-methoxyphenyl, naphthalene ring, oxazole, cyclohexyl, cyclopentyl, methyl, ethyl and isopropyl. A biological activity test result shows that the indole allylamine amide derivative disclosed by the invention has relatively good antagonistic activity on beta2AR and can be used for carrying out negative allosteric regulation on the functional activity of isoproterenol.

Intranasal dry powder epinephrine compositions are described herein. The compositions include epinephrine or a pharmaceutically acceptable salt thereof, as well as a stabilizing agent and a carrier. The stabilizing agent is operable to include citric acid, or a pharmaceutically acceptable salt derived therefrom. Such intranasal compositions as described herein are useful in the treatment of health conditions which threaten the central nervous system (CNS) and impede the actions of alpha and beta-adrenergic receptors. Such health conditions include anaphylaxis, bronchospasms, respiratory impairment, organophosphate poisoning, and major adverse cardiac events (MACE).

Provided is a method and a medicament for treating amyotrophic lateral sclerosis (ALS) in a subject in need thereof, comprising administering to the subject an effective amount of one or more active agents selected from the group consisting of a retinoic acid receptor alpha (RARα) agonist, a voltage-gated potassium channel (KCNB2) inhibitor, an adrenergic receptor α2B (ADRA2B) antagonist, a DNA methyltransferase 3 alpha (DNMT3A) antagonist, an insulin like growth factor 1 receptor (IGF1R) inhibitor, a mitogen-activated protein kinase 1 (MAPK1) inhibitor, a nitric oxide synthase 1 (NOS1) inhibitor, a glucocorticoid receptors (NR3C1) antagonist, and a peptidylprolyl Isomerase A (PPIA) antagonist.

The invention belongs to the field of medicinal chemistry, and particularly discloses a pyrrole amide derivative, a preparation method thereof and application of the pyrrole amide derivative as a beta2-adrenergic receptor allosteric antagonist. The structure of the pyrrole amide derivative is shown as a formula I. In the formula I, R1 is ethyl, methyl, isopropyl and the like; r2 is fatty amine, aniline, m-bromoaniline, benzylamine and the like. Pharmacological results show that the pyrrole amide derivative disclosed by the invention has relatively good antagonistic activity on beta2AR, and can perform negative allosteric regulation on the functional activity of isoprenaline (ISO) serving as a normal agonist of beta2AR.

The application belongs to the field of pharmaceutical chemistry, and specifically discloses a benzimidazole amine derivative, a preparation method thereof and application of the benzimidazole amine derivative as a beta2-adrenergic receptor allosteric antagonist. In the benzimidazole amine derivative, R1 is a hydrogen atom or a bromine atom; and R2 is a substituted benzoyl group or a substituted benzyl group. Pharmacological results show that the benzimidazole amine derivative has good antagonistic activity on beta2AR and can negatively allosterically regulate the functional activity of isoprenaline (ISO).

The invention relates to the field of antibodies, in particular to a monoclonal antibody for treating overactive bladder and application of the monoclonal antibody. The monoclonal antibody specifically recognizes and is combined with an adrenergic receptor beta3 (ADR beta3), the monoclonal antibody is obtained through a hybridoma technology, and the M13 monoclonal antibody with high affinity is successfully screened out. The M13 antibody promotes the increase of cAMP concentration in smooth muscle cells and activates a PKA pathway by activating an ADR beta3 receptor, thereby promoting the relaxation of bladder smooth muscles, increasing the bladder capacity and reducing the non-autonomous contraction of detrusor muscles. Animal experiments prove that the M13 monoclonal antibody can effectively improve the urination frequency and urine volume of a mouse OAB model, and has a good clinical application prospect. The monoclonal antibody and the preparation method thereof can be widely applied to the field of treatment of overactive bladder.

Intranasal dry powder epinephrine compositions are described herein. The compositions include epinephrine or a pharmaceutically acceptable salt thereof, as well as a stabilizing agent and a carrier. The stabilizing agent is operable to include citric acid, or a pharmaceutically acceptable salt derived therefrom. Such intranasal compositions as described herein are useful in the treatment of health conditions which threaten the central nervous system (CNS) and impede the actions of alpha and beta-adrenergic receptors. Such health conditions include anaphylaxis, bronchospasms, respiratory impairment, organophosphate poisoning, and major adverse cardiac events (MACE).

Intranasal dry powder epinephrine compositions are described herein. The compositions include epinephrine or a pharmaceutically acceptable salt thereof, as well as a stabilizing agent and a carrier. The stabilizing agent is operable to include citric acid, or a pharmaceutically acceptable salt derived therefrom. Such intranasal compositions as described herein are useful in the treatment of health conditions which threaten the central nervous system (CNS) and impede the actions of alpha and beta-adrenergic receptors. Such health conditions include anaphylaxis, bronchospasms, respiratory impairment, organophosphate poisoning, and major adverse cardiac events (MACE).

Intranasal dry powder epinephrine compositions are described herein. The compositions include epinephrine or a pharmaceutically acceptable salt thereof, as well as a stabilizing agent and a carrier. The stabilizing agent is operable to include citric acid, or a pharmaceutically acceptable salt derived therefrom. Such intranasal compositions as described herein are useful in the treatment of health conditions which threaten the central nervous system (CNS) and impede the actions of alpha and beta-adrenergic receptors. Such health conditions include anaphylaxis, bronchospasms, respiratory impairment, organophosphate poisoning, and major adverse cardiac events (MACE).

The current methods and compositions involve treating atrial fibrillation with bucetinol after determining that the patient, including the patient with heart failure, is homozygous for Arg389 in the β1-adrenergic receptor gene.

The current methods and compositions relate, in certain aspects, to treatment of atrial fibrillation with bucindolol in patients, including patients with heart failure, after being determined to have non-internalizing ß-adrenergic receptors.

The present invention relates to compounds that are activators of the Alpha1A-Adrenergic Receptor (α1A-AR) and methods of using such compounds: for treating neurological conditions, for cardio-protection, and for treating other conditions. In certain embodiments, the α1A-AR activator compound is a compound of Formula I. In certain embodiments, the neurological condition is Alzheimer's disease, benign prostatic hyperplasia, memory loss, depression, or Parkinson's disease.

The invention belongs to the field of pharmaceutics, particularly relates to a composition containing levosalbutamol hydrochloride and ipratropium bromide as well as a preparation method and application of the composition, and overcomes the defects of a stabilizer disodium ethylene diamine tetraacetate adopted in the prior art. The invention provides a levosalbutamol hydrochloride and ipratropium bromide composition which is simpler in prescription and better in safety, can be used for treating reversible bronchospasm related to airway obstructive diseases, can jointly act on muscarinic acid and beta2 adrenergic receptors in the lung, can enhance the bronchiectasia effect, takes effect quickly, and is free of toxic and side effects. The clinical application value is very high.

The present disclosure is directed to chemical compounds and to the use of such compounds in the treatment of diseases associated with an adrenergic receptor. In certain embodiments of the methods disclosed herein, the methods include administering to the subject a compound as disclosed herein and a peripherally acting P-blocker (PABRA).

The present invention relates to methods and compositions for mobilizing cells in a subject by blocking CXCR4, beta-adrenergic receptor, GPCR, or any combination thereof. In some embodiments, the cells are stem cells. In some embodiments, the cells are immune cells.

The present invention provides a combined ophthalmic pharmaceutical composition of two drugs and a combined composition of three drugs for treating glaucoma and ocular hypertension. The stability of the pharmaceutical composition is greatly improved by salt modification technology. The combined two-drug pharmaceutical composition is produced from netarsudil free base or a pharmaceutically acceptable salt thereof, and an adrenergic β-receptor blocker. The combined three-drug pharmaceutical composition is produced from netarsudil free base or a pharmaceutically acceptable salt thereof, an adrenergic β-receptor blocker, and a prostaglandin analog. The combined pharmaceutical composition of two drugs and three drugs has excellent stability at pH 4.5 to 5.4. By administering an effective amount of the pharmaceutical composition of the present invention once a day to the eyes of patients in need at bedtime or at a time close to bedtime, the intraocular pressure can be effectively and rapidly reduced, and the intraocular pressure can be maintained within the physiological range for a long time. In addition, it has few side effects and high patient compliance.

The present invention relates to a plurality of engineered variants based on muscarinic toxin MT3 which specifically bind to muscarinic acetylcholine receptor M4 or adrenergic receptor alpha 2A, preferably human muscarinic acetylcholine receptor M4 or human adrenergic receptor alpha 2A.

An object of the present invention is to provide a drug evaluation method using myocardial cells, which can stably evaluate an effect of a drug such as a muscarinic receptor agonist, an adrenergic receptor inhibitor or a muscarinic receptor inhibitor on a heart rate; and a reagent and a kit for carrying out the drug evaluation method. According to the present invention, there is provided a drug evaluation method including: treating myocardial cells with a culture medium containing a physiologically active substance of a sympathetic nervous system and / or a physiologically active substance of a parasympathetic nervous system; bringing a drug into contact with the myocardial cells treated as above; and evaluating an effect of the drug on a heart rate of the myocardial cells.

The present disclosure relates to novel alpha2 adrenergic receptor (α2AR) agonists and uses thereof. In particular, the present disclosure relates to imidazole containing compounds, in particular, of formula (I-A), formula (I-B), formula (I-C), formula (I-D), or formula (II). These compounds can be useful as peripherally selective α2AR agonists for the treatment or prevention of disease thereof.

The present invention relates to a combination of a noradrenaline reuptake inhibitor and α2-Adrenoceptor subtype C (alpha-2C) antagonists, in particular substituted heterocyclic carboxamides of formula (I) for the treatment and / or prophylaxis of sleep-related breathing disorders, preferably obstructive and central sleep apneas and snoring.

The present invention relates to novel compounds of formula I or any pharmaceutically acceptable salt, crystal, stereoisomer, hydrate, solvate, prodrug, metabolite or solvate thereof. Among other properties, the compounds of the invention exhibit long-acting muscarinic antagonism (LAMA) or dual pharmacological activity at the muscarinic M3 receptor and the beta-2 adrenergic receptor (MABA), which are useful for the treatment of respiratory conditions, such as asthma, chronic obstructive pulmonary disease (COPD) and rhinitis for example. The invention encompasses the compounds, reagent and intermediate compounds, processes for obtaining the compounds of the invention, pharmaceutical compositions, combinations and medicaments containing them and their therapeutic uses and methods for the treatment of human diseases in which such receptors are involved. formula (I)