Abstract: The present invention is directed to compounds of Formula I: I (where variables A1, A2, B, J, K, m, n, R4, R5a, R5b and R5c are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache.

Abstract: The present invention relates to a stable pharmaceutical composition of a combination of amlodipine and an ACE inhibitor; wherein the two active ingredients are not physically separated and the composition has a pH of more than 6.0. It also relates to a process for preparation, and a method for using such a composition.

Abstract: A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.

Abstract: A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

Abstract: The present invention is directed to the use of benzethonium chloride, alone or in combination with phenoxyethanol or phenyl ethyl alcohol, to provide anti-microbial activity in pharmaceutical compositions. The present invention also provides methods of using benzethonium chloride, alone or in combination with phenoxyethanol or phenyl ethyl alcohol, to inhibit microbial growth in pharmaceutical compositions.

Abstract: Novel multibinding compounds are disclosed. The compounds of this invention comprise 2–10 ligands covalently connected, each of the ligands being capable of binding to a ligand binding site in a Ca++ channel, thereby modulating the biological activities thereof.

Abstract: This invention relates to novel cyclic malonamides having the formula (I): to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A?-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to ?-amyloid production such as Alzheimer's disease and Down's Syndrome.

Abstract: A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

Abstract: Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I: wherein R3, R4, R5, W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described.

Abstract: The present invention relates to use of compounds represented by the following general formula [1] or salts or prodrugs thereof: [where R1 represents hydrogen atom or lower alkoxy group; R2 represents hydrogen atom, lower alkoxy group, optionally substituted phenyl group, (where R3 represents acyl group); X represents —CO— or —CH2—; and n-represents 1 or 2], as drugs for overcoming a resistance to anticancer drugs or drugs for enhancing an effect of anticancer drugs. The compounds represented by the general formula [1] have not only a function of overcoming the resistance to various anticancer drugs but also a function of enhancing the effect of various anticancer drugs to anticancer-drug sensitive cells. Thus, these compounds have excellent effects on resistant cells and also on sensitive cells, and in particular effective in the treatment of a cancer having an acquired resistance to an anticancer drug.

Abstract: Compounds having the general formula wherein R1a, R1b, R1c, X1, X2, R2, R3, R4, R5, R6, n, Y and Z are as defined in the specification, methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.

Abstract: Novel multibinding compounds are disclosed. The compounds of this invention comprise 2-10 ligands covalently connected, each of the ligands being capable of binding to a ligand binding site in a Ca++ channel , thereby modulating the biological activities thereof.

Abstract: Compounds of structural Formula (I) where A is a lipophilic group including an aliphatic bridging group, B is a lipophilic group, D is a group having at least one amino or substituted amino group and R is hydrogen, alkyl or cycloalkyl, and pharmaceutically acceptable salts and individual isomers thereof, which have growth hormone releasing activity in humans or animals

Abstract: The present invention is directed to an inhalable formulation for the treatment of pulmonary hypertension in a mammal (e.g., humans), wherein the formulation comprises at least one hypertension reducing agent, including but not limited to an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, calcium-channel blocker or vasodilator, or any combination thereof. The formulations of the present invention may be a solution or suspension, and preferably are suitable for administration via nebulization. The present invention is also directed to a method and kit for treating a mammal suffering from pulmonary hypertension.

Abstract: The invention is of a non-invasive, topical medicament and associated methodology for use thereof, through the use of which existing scars may be effectively, cost effectively, and painlessly treated. One or more calcium channel blocker agents serve as the primary active ingredient of the present compositions and transdermal penetration agents or carriers are included to facilitate topical delivery of the active ingredient(s) to the intended, sub-dermal treatment site.

Abstract: Novel multibinding compounds are disclosed. The compounds of this invention comprise 2-10 ligands covalently connected, each of the ligands being capable of binding to a ligand binding site in a Ca++ channel, thereby modulating the biological activities thereof.

Abstract: A method of treating or preventing myocardial ischemia in a patient in need thereof comprising administration of a controlled-release Galenical preparation of pharmaceutically acceptable Diltiazem including the pharmaceutically acceptable salts thereof, suitable for evening dosing every 24 hours containing from about 180 mg to about 420 mg of the form of Diltiazem associated with excipients to provide controlled (sustained) release of the form of Diltiazem for providing a Cmax of Diltiazem in the blood at between about 10 hours and about 17 hours after administration, the preparation comprising the form of Diltiazem in oral sustained-release dosage form in which the Diltiazem is adapted to be released after administration over a prolonged period of time and exhibits when given to humans

Abstract: The use of calcium channel blockers administered intra-nasally to inhibit olfactory sensory perception to treat eating disorders, including obesity, is described. Also described is a method of reducing food intake in a subject by administering a pharmaceutical composition comprising an effective amount of a calcium channel blocker to the nasal mucosa, as well as screening methods for drugs to be used in treating obesity or associated disorders.

Abstract: An improved method for using a NNRTI in the treatment of HIV-1 infection, comprising administering to a human, needing treatment for HIV-1 infection, a therapeutically effective amount of said NNRTI or a pharmaceutically acceptable salt thereof, and an amount of an inhibitor of the cytochromes P450 that is sufficient to elevate, enhance, or extend plasma concentrations of said NNRTI.

Abstract: A vasectomy procedure is performed using a vas irrigation solution having a spermicidal agent that (a) acts to reduce the viability of downstream sperm following a vasectomy procedure and (b) has been established as safe and non-toxic in humans when administered by intravenous or other routes of injection for the treatment of other conditions. Preferred spermicidal agents are methylene blue and diltiazem. A kit having a pair of single-use, pre-filled injection devices is also disclosed.

Abstract: A device and method is described for providing sustained vasodilation at a site in a patient. The device includes a biocompatible and possibly biodegradable carrier, and a vasodilator incorporated into the carrier. The vasodilator is present in a topically effective amount to achieve sustained vasodilation at a selected site in a patient. The vasodilator may be nitroglycerine or calcium channel blockers. The carrier includes methylcellulose and equine collagen, and may be in the form of a strip. The method includes administering, at a selected site in a patient, a vasodilator incorporated into a carrier. The vasodilator is present in a topically effective amount to achieve sustained vasodilation at the selected site.

Abstract: Novel cyclic malonamides having the formula (I): and their pharmaceutical compositions. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A&bgr;-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein.

Abstract: The present invention relates to the delivery of a migraine headache drug through an inhalation route. Specifically, it relates to aerosols containing a migraine headache drug that are used in inhalation therapy. In a method aspect of the present invention, a migraine headache drug is administered to a patient through an inhalation route. The method comprises: a) heating a composition, wherein the composition a migraine headache drug, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles aerosol comprising particles with less than 5% drug degradation products. In a kit aspect of the present invention, a kit for delivering a migraine headache drug through an inhalation route is provided which comprises: a) a thin coating of an a migraine drug composition and b) a device for dispensing said thin coating as a condensation aerosol.

Abstract: The present invention relates to the delivery of anti-migraine compounds through an inhalation route. Specifically, it relates to aerosols containing lidocaine, verapamil, diltiazem, isometheptene, or lisuride that are used in inhalation therapy. In a method aspect of the present invention, lidocaine, verapamil, diltiazem, isometheptene, or lisuride is administered to a patient through an inhalation route. The method comprises: a) heating a composition of lidocaine, verapamil, diltiazem, isometheptene, or lisuride, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles with less than 5% drug degradation products.

Abstract: The present invention relates to methods of treating sexual dysfunction associated with hypertension and another condition by administering a pharmaceutical combination of an angiotensin receptor blocker with either an anti-hypertensive drug or an HMG-CoA reductase inhibitor.

Abstract: A dosage formulation for once daily administration prior to sleeping is described that provides an initial delay in pharmaceutical release followed by controlled release of the pharmaceutical. There is also provided a method for preparing a time specific delayed, controlled release formulation of dosage, which method includes coating a single pellet with at least one dosage layer, which is coated by at least one seal coat and at least one outer rate controlling layer of a water soluble polymer coat. The dosage formulation of this invention provides a substantially drug free interval of about 0 to 5 hours followed by a drug delivery interval at a rate permitting bioavailability thereof for up to about 24 hours following oral administration. A method of using the formulations of the present invention for the treatment of early morning pathologies, including atrial fibrillation, is also described.

Abstract: The invention concerns the use of a calcium channel blocker compound and/or cyclic GMP-dependent channels, namely diltiazem, for treating retinal pathologies, and more particularly retinal diseases caused by degeneration of visual receptors, in a human or animal.

Abstract: A pharmaceutical composition comprising at least one pharmaceutically active agent that is pH dependent, at least one non-pH dependent sustained release agent, and at least one pH dependent agent that increases the dissolution rate of the at least one pharmaceutically active agent at a pH in excess of 5.5. Such compositions have minimized pH-dependent dissolution profiles or pH-independent dissolution profiles.

Abstract: Smooth muscle tone modulator compositions and methods of use thereof are provided for the treatment of oesophageal motility disorders and gastro-oesophageal reflux disease. The smooth muscle tone modulators are applied topically to treat the disorder. Topical treatment reduces the risk of undesirable side effects observed in connection with oral or sublingual administration of the modulators.

Abstract: The invention relates to a pharmaceutical formulation containing at least one compound of formula (1) wherein R1, R2, and X have the same meaning as cited in claim 1, and the physiologically acceptable salts thereof and/or solvates and a) at least one antithrombotic or b) at least one calcium antagonist or c) at least one prostaglandin or prostaglandin derivative for producing a medicament for treating angina, high blood pressure, pulmonary hypertension, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), pulmonary heart disease, right ventricular failure, atheriosclerosis, permeability conditions of reduced cardiovascular patency, peripheral vascular illnesses, cerebral apoplexy, bronchitis, allergic asthma, chronic asthma, allergic rhinitis, glaucoma, irritable bowel syndrome, tumours, kidney failure, cirrhosis of the liver and for treating female sexual problems.

Abstract: The present invention provides compositions and methods for using cardioprotective or hemodynamic drugs in combination with dichloroacetate enabling usage of cardioprotective or hemodynamic drugs at concentrations higher than used in normal clinical practice without increasing deleterious side effects normally associated with the cardioprotective or hemodynamic drug, thereby conferring added clinical benefit. The present invention teaches administration of DCA with cardioprotective or hemodynamic drugs as an adjunct therapy thereby conferring added clinical benefit to clinically recommended protocols.

Abstract: An anti-muscarinic agent and a calcium channel blocker are suitable for simultaneous, sequential or separate use in the treatment of a muscle tone disorder or a proliferative, inflammatory or secretory condition.

Abstract: The invention provides methods and compositions for treatment of tumors comprising administering to subject bearing a tumor an effective amount of at least one agent that decreases the [GSH]2/[GSSG] ratio in the malignant cells of said tumor, wherein said at least one agent is administered continuously to said patient for a period of time within the range of from about 15 to about 75 hours.

Abstract: The present invention provides a controlled release device for sustained or pulsatile delivery of pharmaceutically active substances for a predetermined period of time. This invention further provides such device in which sustained or pulsatile delivery is obtained by the unique blend and Inmate mixture of pharmaceutically active substances with a microbial polysaccharide and uncrosslinked linear polymer and optionally a crosslinked polymer and/or lipophillic polymer and/or saturated polyglycolyzed glyceride. The invention also provides a process for the manufacture of such devices and pharmaceutical compositions containing the same.

Abstract: A pharmaceutical composition which comprises a chemotherapeutically effective amount of one or more chemotherapeutic agent(s), being entrapped in a drug carrier, and a chemosensitizing effective amount of one or more chemosensitizing agent(s) and/or a chemoprotecting effective amount of one or more chemoprotecting agent(s) and methods of using same in cancer therapy.

Abstract: A sustained-release pharmaceutical preparation is disclosed in which a calcium channel blocker, preferably verapamil, core is surrounded by an optional seal coat layer and a water-insoluble coating.

Abstract: Compositions and methods for vaginal, buccal or nasal transmucosal delivery of drugs and for cryoprotecting of cells and embryos. For cryoprotection, the composition consisting essentially consist of a non-ionizable glycol derivative. For transmucosal delivery, the compositions essentially consist of a non-ionizable glycol derivative in a combination with a pharmaceutically active agent. For transmucosal delivery, the non-ionizable glycol derivative may be further combined with a mucoadhesive agent and/or a penetration enhancer and/or lipophilic or hydrophilic carrier for adhesion to and transport through a mucosa. The compositions are particularly suitable for administration of drugs through a nasal, buccal and vaginal mucosa or for long-term preservation of cell or embryos.

Abstract: A multiplex drug delivery system suitable for oral administration containing at least two distinct drug dosage packages, which exhibit equivalent dissolution profiles for an active agent when compare to one another and when compared to that of the entire multiplex drug delivery unit, and substantially enveloped by a scored film coating that allows the separation of the multiplex drug delivery system into individual drug dosage packages can provide a convenient and cost effective drug delivery unit, particularly for patients with a regimen of prescribed dosages that varies during their treatment period.

Abstract: This invention relates to pharmaceutical combinations of atorvastatin or a pharmaceutically acceptable salt thereof and antihypertensive agents, kits containing such combinations and methods of using such combinations to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and to treat subjects presenting with symptoms of cardiac risk, including humans. This invention also relates to additive and synergistic combinations of atorvastatin or a pharmaceutically acceptable salt thereof and antihypertensive agents whereby those synergistic combinations are useful in treating subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and those subjects presenting with symptoms of cardiac risk, including humans.

Abstract: Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formulas and their enantiomers, diastereomers, and their pharmaceutically acceptable salts, including prodrugs and solvates thereof wherein: r, s and t are 0 or 1; m=0, 1, 2; p is 0, 1 or 2; X is selected from the group consisting of oxygen, hydrogen or R1, R2, R3; Y is selected from the group consisting of CHR9, SO2, CO, CO2, O, NR10, SO2NR11 and CONR12; R6, R7, R9, R10, R11, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, and R28 are selected from the group consisting of hydrogen, lower alkyl or substituted alkyl; R4, R5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R13; R12 is selected from the group consisting of hydrogen, lower alkyl, aryl, substituted alkyl or aryl; U is selected from the group consisting of sulfur, oxygen, NR14, CO, SO, SO2, CO2, NR15CO2, NR16CONR17, NR19SO2, NR19SO2NR20, SO2NR2

Abstract: Disclosed is a method for prophylactic or therapeutic treatment of a condition or disease responsive to opening of ClC-2 channel, which comprises the step of administrating an effective amount of a ClC-2 channel opener to a subject in need of said treatment. According to the invention, a tissue or organ to be transplanted can also be treated with the ClC-2 channel opener.

Abstract: The invention is of a medicament and associated treatment involving the use of such medicament for the treatment of vulvodynia. The medicament is in the dosage form of a vaginal suppository, and the primary active ingredient is a calcium antagonist—Diltiazem Hydrochloride in the preferred embodiment.

Abstract: A pharmaceutical composition comprising as its active ingredients one or more drugs selected from the group consisting of angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors, and one or more insulin resistance improving agents exhibits excellent arteriosclerotic progress inhibitory effects, and is useful as a drug, particularly as a drug for the prevention or treatment of arteriosclerosis. The invention also provides a method for the treatment or prophylaxis of arteriosclerosis by administering in combination (i) at least one of said angiotensin II receptor antagonists or angiotensin converting enzyme inhibitors and (ii) one or more insulin resistance improving agents to a mammal suffering from or susceptible to arteriosclerosis.

Abstract: Pyridazino(4,5-b)(1,5)oxazepinone, thiazepinone and diazepinone compounds of formula(I) and their tautomers and the acid-addition salts of all these compounds show memory-enhancing and neuroprotective properties.

Abstract: The present invention relates to zero-order sustained release solid dosage forms suitable for administration of a wide range of therapeutically active medicaments, especially those that are water-soluble, and to a process of making same. The solid dosage form comprises (a) a matrix core comprising ethylcellulose and the active agent and (b) a hydrophobic polymer coating encasing the entire matrix core.

Abstract: The invention relates to a pharmaceutical composition for relieving pelvic pain or infertility associated with uterine dysrhythmia. The composition includes a locally-administered anti-dysrhythmic treating agent and a bioadhesive extended-release carrier. The composition may be delivered in an extended release formulation that includes a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer, such as polycarbophil. The treating agent may be a local anesthetic, such as lidocaine. The invention also relates to a method of treating or preventing pelvic pain, or treating or improving infertility, by inserting a mixture of an anti-dysrhythmic treating agent and a bioadhesive carrier into the vagina of the patient to be treated.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.