Abstract: NHE-1 inhibitors, methods of using such NHE-1 inhibitors and pharmaceutical compositions containing such NHE-1 inhibitors. The NHE-1 inhibitors are useful for the reduction of tissue damage resulting from tissue ischemia.

Abstract: This invention relates to compounds of the formula and to pharmaceutically acceptable salts and solvates thereof, wherein a, b, X, Y, Z, R1, R2, and R3 are as defined herein. The compounds of formula I are antibacterial and antiprotozoal agents useful for treating various bacterial and protozoal infections and disorders related to such infections. The invention also relates to pharmaceutical compositions containing the compounds of formula I, to methods of treating bacterial and protozoal infections by administering the compounds of formula I, and to methods for preparing compounds of formula I.

Abstract: This invention relates to compounds of formula (I), wherein A, B, D, E, K, G, Z, R3 and R5 are defined as in the specification, and to the pharmaceutically acceptable salts of such compounds. Compounds (I) are corticotropin releasing factor (hormone) CRF (CRH) antagonists.

Abstract: The present invention relates to a method of treating sleep disorders including sleep apnea in a mammal, including a human, by administering to the mammal a 5HT1a antagonist or an alpha-2-adrenergic antagonist in combination with an SRI antidepressant agent with improvement in efficacy. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a 5HT1a antagonist or an alpha-2-adrenergic antagonist, and an SRI antidepressant agent.

Abstract: A method and device for the automated large scale preparation for testing of drug-drug interactions, particularly with determination of IC50 and Ki, as a screening tool enhancement for determining viability of large numbers of compounds as drug candidates. Small samples of specific probe substrates and new compound inhibitors are automatically dispensed en masse into multi-welled reaction plates which are prefilled with thawed human microsomes, buffer and cofactor. The reaction plates are incubated and the reaction products are tested within degradation time limits, for initial biological determinations of relevant interaction effects of the compounds.

Abstract: This invention relates to novel nucleic acid sequences encoding three novel human phosphodiesterase (hPDE IV) isozymes. It also relates to polypeptides encoded by such sequences. This invention also relates to an assay method for detecting the presence of such novel isozymes in human cells, and to a method of identifying compounds or other substances that inhibit or modify the activity of such isozymes.

Abstract: Cholesteryl ester transfer protein inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

Abstract: The present invention relates to a method of treating disorders of the central nervous system (CNS) and other disorders in a mammal, including a human, by administering to the mammal a CNS-penetrant &agr;7 nicotinic receptor agonist. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier and a CNS-penetrant &agr;7 nicotinic receptor agonist.

Abstract: The present invention relates to a novel process for the preparation of a diastereomeric mixture of piperidinylaminomethyl trifluoromethyl cyclic ether compounds of formulae Ia and Ib: and pharmaceutically acceptable salts thereof, wherein R1 is C1-C6 alkyl; R2 is C1-C6 alkyl, halo C1-C6 alkyl or phenyl or substituted phenyl; R3 is hydrogen or halo; m is zero, one or two, and wherein said mixture is highly enriched in the compound of formula Ia, and to novel processes for the preparation and purification of intermediate compounds useful in the preparation of compounds of formulae Ia and Ib.

Abstract: This invention relates to mutual prodrugs of amlodipine and atorvastatin and to pharmaceutical compositions thereof. This invention also relates to methods of treating angina pectoris, atherosclerosis, and hypertension and hyperlipidemia in a mammal using those prodrugs and compositions. This invention also relates to methods of managing cardiac risk in a mammal, including humans, presenting with symptoms of cardiac risk by administering those prodrugs and compositions.

Abstract: The present invention provides polynucleotide molecules comprising nucleotide sequences encoding plasminogen activating (PauA) proteins from Streptococcus uberis, and substantially homologous polypeptides, peptide fragments, and fusion proteins thereof. The present invention further provides compositions and methods for recombinantly expressing the PauA proteins, substantially homologous polypeptides, peptide fragments and fusion proteins encoded by the polynucleotide molecules of the present invention. The present invention further provides a vaccine for protecting a member of a mammalian species against mastitis, comprising a PauA protein, substantially homologous polypeptide, peptide fragment, fusion protein, or polynucleotide molecule of the present invention.

Abstract: This invention provides compounds of formula I and pharmaceutically-acceptable salts thereof, where the substituents are defined in the specification, which are growth hormone secretogogues useful for treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength , mobility, maintenance of skin thickness, metabolic homeostatis or renal homeostasis. Compounds of formula I in combination with: a bisphosphonate such as alendronate; estrogen, estrogens, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions thereof are useful in treating osteoporosis.

Abstract: The invention relates to compounds of the formula and to pharmaceutically acceptable salts thereof, wherein R1 and R2 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1, methods of using said compounds of formula 1 in the treatment of infections, and methods of preparing said compounds of formula 1.

Abstract: Four antigenic preparations are provided, each of which contains a different protein from Leptospira which can be used immunologically in vaccines for leptospirosis caused by this organism. Also provided in the invention are polynucleotides encoding these four proteins and antibodies which bind the proteins for use in the diagnosis of leptospirosis.

Abstract: The present invention relates to the compound (+)-6-[amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1-cyclopropylmethyl-1H-quinolin-2-one, pharmaceutically acceptable salts and solvates thereof, prodrugs thereof, and to the use of said compound for inhibiting abnormal cell growth, including cancer, in mammals. The invention also relates to methods useful in synthesizing the aforementioned compound.

Abstract: There is provided a compound of formula I, wherein R1, R2, R3, X and Y have meanings given in the description, which are useful in the prophylaxis and in the treatment of pruritus.

Abstract: The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a GABA-A alpha ⅔ agonist in combination with an SRI antidepressant agent with improvement in efficacy. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a GABA-A alpha ⅔ agonist, and an SRI antidepressant agent.

Abstract: A composition comprising eletriptan and a p-glycoprotein (p-gp) inhibitor useful for the treatment of migraine. The bioavailability of eletriptan can be increased by co-administering eletriptan with a p-gp inhibitor. The eletriptan and p-gp inhibitor can be administered together in a composition or as separate components. If administered separately, they can be embodied as a kit. Also provided is a method of treating migraine using said composition or sequential administration of components.

Abstract: The present invention relates to a method of treating migraine in a mammal, including a human, by administering to the mammal a 5HT1 receptor agonist in combination with caffeine and a cyclooxygenase-2 (COX-2) inhibitor. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a 5HT1 receptor agonist with caffeine and a cyclooxygenase-2 (COX-2) inhibitor.

Abstract: The present invention relates to mammalian cell lines which efficiently support the growth and productive infection of Marek's Disease Virus at high titers. The present invention also relates to mammalian cell lines which have been engineered to support the growth and productive infection of recombinant Marek's Disease Virus at high titers. The present invention relates a process for the preparation of Marek's Disease Virus in quantities suitable for vaccine purposes.