Opioid-free, anesthetic, analgesic, antalgesic, anti-nociceptive, anti-inflammatory, antiemetic formulations, and methods for reducing pain, controlling pain, preventing pain, reducing or eliminating exposure to opioids, decreasing nausea and vomiting, featuring administration of the anesthetic/analgesic formulations. The opioid-free/sparing anesthetic/analgesic formulations comprise a local anesthetic, a cyclooxygenase (COX) inhibitor, and an alpha agonist. The formulations may optionally comprise additional compositions including but not limited to NMDA receptor antagonists, Buprenorphine, Dexketoprofen, Carprofen, an antifibrinolytic, an antibiotic, a steroid, a cyclooxygenase 3 inhibitor, a Transient Receptor Potential Vanilloid (TRPV) receptor agonist or antagonist, a protein kinase inhibitor, a competitive or non-competitive glycine or glutamate agonist, a glutamate or glycine inhibitor or antagonist, a neurokinin-1 receptor antagonist, an alpha agonist, a second alpha agonist, and combinations thereof. The formulations are effective for significantly reducing postoperative nausea and vomiting and enhancing postoperative pain relief as compared to existing prior art anesthetics/analgesics.

The present disclosure relates to a pharmaceutical composition for preventing or treating statin-induced adverse effects or a pharmaceutical composition for co-administration with statin, the pharmaceutical composition containing, as an active ingredient, at least one selected from the group consisting of an isoprenoid-based compound, zaragozic acid, terbinafine, and ketoconazole. The pharmaceutical composition according to the present disclosure may prevent and/or treat adverse statin effects that can be induced by statin, that is, can be induced at any time by oxisterols present at abnormal levels in the body. The pharmaceutical composition can not only treat but also prevent the adverse effects of various statin therapeutics whose use has recently increased rapidly, and thus it is expected that the pharmaceutical composition can be widely used for various diseases and the utilization thereof can further be increased.

An RNA methyltransferase inhibitor comprising sulfonamide-based compounds and/or pyrazoline-based compounds is provided

An RNA methyltransferase inhibitor comprising sulfonamide-based compounds and/or pyrazoline-based compounds is provided

The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: ##STR00001##
wherein A, B, X, Y, L.sup.1, L.sup.2, L.sup.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: ##STR00001##
wherein A, B, X, Y, L.sup.1, L.sup.2, L.sup.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABA.sub.A agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABA.sub.A receptor in dorsal root ganglion neurons in the subject using a vector.

The compounds of the invention as shown by general structure I, as shown below, are effective in treating filovirus infections. ##STR00001## X is selected from the group consisting of O and H; R.sup.1 is selected from (C.sub.6 to C.sub.10) aryl and (C.sub.2 to C.sub.9) heteroaryl, and R.sup.2 is selected from (C.sub.1 to C.sub.10) alkyl, (C.sub.1 to C.sub.10) alkenyl, (C.sub.1 to C.sub.10) alkynyl, (C.sub.3 to C.sub.10) cycloalkyl, and (C.sub.5 to C.sub.10) cycloalkenyl, and NR.sup.3aR.sup.3b is defined in the specification. These compounds are effective in treating filovirii infections including Ebolavirus and Marburg virus.

The compounds of the invention as shown by general structure I, as shown below, are effective in treating filovirus infections. ##STR00001## X is selected from the group consisting of O and H; R.sup.1 is selected from (C.sub.6 to C.sub.10) aryl and (C.sub.2 to C.sub.9) heteroaryl, and R.sup.2 is selected from (C.sub.1 to C.sub.10) alkyl, (C.sub.1 to C.sub.10) alkenyl, (C.sub.1 to C.sub.10) alkynyl, (C.sub.3 to C.sub.10) cycloalkyl, and (C.sub.5 to C.sub.10) cycloalkenyl, and NR.sup.3aR.sup.3b is defined in the specification. These compounds are effective in treating filovirii infections including Ebolavirus and Marburg virus.

This invention concerns a dosage form comprising a therapeutically effective amount of A19-144 or A2-73 and a therapeutically effective amount of at least one AED. This invention further encompasses a method of treating a subject in need of such treatment comprising administering a therapeutically effective amount of A19-144 or A2-73 in conjunction with any therapeutically effective amount of an AED.