West Virginia University

The University of Mississippi

L'universitÉ Catholique De Louvain

Other

University System of Maryland

Rae Matsumoto

Scott Pollard

Patrick Marshalek

Christophe Mesangeau

Christopher R McCurdy

Jacques Henri Poupaert

Alexander D MacKerell, Jr

Mark T Hamann

Andrew Coop

Bonnie Ann Avery

Ahmed Hassan Amin Abdelazeem

Anna J Kochanowska

Abir El-Alfy

Sanju Narayanan

Angelo Boujos

The present invention provides a method of treating depression disease in a treatment resistant patient comprising administering to a mucosal membrane of a patient an effective amount of a pharmaceutically acceptable composition comprising an effective amount of ketamine or dextromethorphan, wherein the mucosal administration of the ketamine or dextromethorphan containing composition allows for the mucosal absorption of the composition eliminating the digestive tract of the patient for effecting a rapid acting antidepressant treatment of the treatment resistant patient. This method includes administering the composition to a patient's mucosal membrane of a respiratory tract, a genitourinary tract, an oral tract, or rectal tract of the patient. A pharmaceutically acceptable composition comprising ketamine or dextromethorphan and a vehicle is disclosed. A biomarker for identifying a depressive disease is set forth.

Ketamine or dextromethorphan formulations and methods of use

The present invention provides a method of treating depression disease in a patient comprising administering to a mucosal membrane of a patient an effective amount of a pharmaceutically acceptable composition comprising an effective amount of ketamine or dextromethorphan, or both ketamine and dextromethorphan, wherein the mucosal administration of the ketamine or dextromethorphan containing composition allows for the mucosal absorption of the composition eliminating the digestive tract of the patient for effecting a rapid acting antidepressant treatment of the patient. Preferably, this method includes administering the composition to the oral cavity, and more preferably to the buccal cavity, of the patient. A pharmaceutically acceptable composition comprising ketamine or dextromethorphan and a vehicle is disclosed. A biomarker for identifying a depressive disease is set forth. A method of treating depressive illness in a patient using dextromethorphan via the oral route is provided.

An opioid narcotics used for the treatment of moderate-to-severe pain that primarily exert their analgesic effects through &#x3bc; receptors. Although, traditional &#x3bc; agonists can cause undesired side effects, including tolerance, addition of &#x3b4; antagonists can attenuate said side effects. The present invention includes 4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor, along with analogs of morphine, dihydromorphine, hydromorphone, codeine, dihydrocodeine, hydrocodone and ethylmorphine. Although UMB 425 lacks &#x3b4;-specific motifs, conformationally sampled pharmacophore models for &#x3bc; and &#x3b4; receptors predict it to have efficacy similar to morphine at &#x3bc; receptors and similar to naltrexone at &#x3b4; receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols. UMB 425 exhibits a mixed &#x3bc; agonist/&#x3b4; antagonist profile as determined in receptor binding. UMB 425 has mixed &#x3bc; agonist/&#x3b4; antagonist properties in vitro that translate to reduced tolerance liabilities in vivo.

Mixed &#x3bc; agonist/ &#x3b4; antagonist opioid analgesics with reduced tolerance liabilities and uses thereof

A compound useful for treating subjects in need of therapy involving sigma receptors or for alleviation of affects resulting from drug abuse having the general formula I in which Rcan be a radical of an optionally substituted C-4 to C-7 N-containing heterocycle such as, for example, radicals of optionally substituted piperidines, optionally substituted piperazines, optionally substituted tetrahydropyridines, optionally substituted azepanes, tertiary amines (cyclic or acyclic), isoindoline-1,3-dione, or optionally substituted tetrahydroisoquinolones (aromatically substituted): Rcan each independently be any one or combinations of the following moieties, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; Y can be either CH, CH, O, S, OCH, N&#x2014;R, N&#x2014;Ar, C&#x2014;R, C&#x2014;Ar; Z can be either H, O, S, S&#x2014;R or NR. R groups can be either H, aryls, alkyls, or cycloalkyls; 'n' can be 1 to 5 carbons in length and stereoisomers, functional analogs, and pharmaceutically acceptable salts thereof and wherein the moiety bridging Rand N can be optionally substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene and where the alkylene group can include an inserted C-Ccycloalkyl group, aromatic and heterocyclic group.

Highly selective sigma receptor ligands

Compounds having the general formula II, III, or IV wherein Rcan be a radical of an optionally substituted C-4 to C-7 N-containing heterocycle or a radical of an optionally substituted cyclic or acyclic tertiary amine or isoindoline-1,3-dione: Rcan each independently be any one or combinations of the following moieties, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate, optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; Y can be either CH, CH, O, S, OCH, N&#x2014;R, N&#x2014;Ar, C&#x2014;R, C&#x2014;Ar; Z can be either H, O, S, S&#x2014;R or NR. R groups can be either H, aryls, alkyls, or cycloalkyls; 'n' can be 1 to 5 carbons in length and stereoisomers, functional analogs, and pharmaceutically acceptable salts thereof and wherein the moiety bridging Rand N can be a substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene and where the alkylene group can include an inserted C-Ccycloalkyl group, aromatic, and hetercocyclic group; wherein X' is halogen, or C-Chaloalyl; wherein the Ris a C-Cstraight chain or branched chain alkyl or a C-Cstraight chain or branched chain haloalkyl.

The sponges were collected from a variety of locations in the Florida Keys and separated based on morphology and color. The samples were identified as three species, two of which are well known:(Esper, 1794) (order Verongida, family Aplysinidae) and(Hyatt, 1875) (order Dictyoceratida, family Thorectidae), and a third(Duchassaing & Michelotti, 1864), is less common and separated based on subtle differences of morphology and coloration, from the other two species. Several compounds were isolated and were evaluated in established animal models predictive of neurological related drug function, namely, the rodent FST and the chick anxiety-depression model.

Method to use compositions having antidepressant anxiolytic and other neurological activity and compositions of matter

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Morgantown, WV, United States of America

Rae Matsumoto