Research Triangle Institute

University of Arkansas

US Government as Represented by the Secretary of the Army

The United States of America as Represented by the Department of Health

The United States of America Represented by the Secretary of Health and

Philip Abraham

Frank Ivy Carroll

Anita H Lewin

Michael J Kuhar

John W Boja

Samuel Michael Owens

Bruce Edward Blough

Peter K Chiang

Felipe N Padilla

Joh W Boja

Hern&aacute;n A Navarro

Michelle M Richard

Desong Zhong

The invention provides bupropion analogue compounds capable of inhibiting the reuptake of one or more monoamines. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin. Such compounds may be used to treat conditions that are responsive to inhibition of the reuptake of monoamines, including addiction, depression, and obesity.

Monoamine reuptake inhibitors

The invention provides bupropion analog compounds capable of inhibiting the reuptake of one or more monoamines. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin. Such compounds may be used to treat conditions that are responsive to inhibition of the reuptake of monoamines, including addiction, depression, and obesity.

The invention generally relates to hapten compounds comprising either (+) methamphetamine or (+) amphetamine conjugated to a linker. Generally speaking, hapten compounds of the invention may be used to elicit an immune response to one or more of (+) methamphetamine, (+) amphetamine, or (+) MDMA.

Methamphetamine-like hapten compounds, linkers, carriers and compositions and uses thereof

A class of binding ligands for cocaine receptors and other receptors in the brain. Specifically, a novel family of compounds shows high binding specificity and activity, and, in a radiolabeled form, can be used to bind to these receptors, for biochemical assays and imaging techniques. Such imaging is useful for determining effective doses of new drug candidates in human populations. In addition, the high specificity, slow onset and long duration of the action of these compounds at the receptors makes them particularly well suited for therapeutic uses, for example as substitute medication for psychostimulant abuse. Some of these compounds may be useful in treating Parkinson's Disease or depression, by virtue of their inhibitory properties at monoamine transporters.

Cocaine receptor binding ligands

The present invention provides synthetic immunochemical haptens for the generation of antibodies that are designed to recognize the common molecular features of d-methamphetamine-like abused stimulants with insignificant cross-reactivity to endogenous substrates (e.g. dopamine) or over-the-counter medications (e.g. 1-methamphetamine, pseudoephedrine, phenylpropanolamine and ephedrine). These monoclonal antibodies and their antigen binding fragments are useful in treatment plans for recovering addicts, in emergency room settings for rapidly reversing a drug overdose, in protection of fetuses from drug-abusing pregnant mothers or in a psychiatric setting to reduce the exacerbation of psychotic disorders caused by stimulant drugs.

Monoclonal antibody antagonists for treating medical problems associated with d-amphetamine-like drugs

Tropane derivatives having a high binding affinity and selectivity for dopamine transporters bear, on the tropane backbone either a carboxylic ester or isoxazole moiety, as well as a substituted phenyl moiety. The compounds have utility both as pharmaceutical and as imaging agents, when one or more atoms are radioactive.

The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases or in determining the doses of therapeutic agents that occupy significant numbers of receptors.

The invention includes synthetic immunochemical haptens for the generation of antibodies, the antibodies, and the medical treatment applications for using the antibodies. The antibodies are designed to recognize the common molecular features of d-methamphetamine-like abused stimulants, and will have insignificant cross-reactivity with endogenous substrates (e.g. dopamine) or over-the-counter medications (e.g. 1-methamphetamine, pseudoephedrine, phenylpropanolamine and ephedrine). These monoclonal antibodies and their antigen binding fragments are useful in treatment plans for recovering addicts, in emergency room settings for rapidly reversing a drug overdose, in protection of fetuses or fetus from drug-abusing pregnant mothers or in a psychiatric setting to reduce the exacerbation of psychotic disorders caused by stimulant drugs.

The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases.

Ligands for nAChRs are provided based on various derivatives of methyllycaconitine (MLA) such as radiolabeled MLA, and MLA containing a fluorimetric marker group and their use in imaging for detection of Alzheimer's and other CNS diseases, and combinatorial assays for detection of compounds having affinity for nAChRs, as well as injectable compositions containing the same and kits for performing the imaging studies.

Ligands for &agr;-7 nicotinic acetylcholine receptors based on methyllcaconitine

The 3&agr; isomer of RTI-55, RTI-352, is an effective in vivo binding ligand that reflects greater selectivity for the dopamine transporter than is observed with RTI-55. In addition, there is also a more rapid achievement of apparent equilibrium in the striatal-to-cerebellar ratio (compared to RTI-55) as the ratio peaks at about 30 min and is maintained for about 20 min thereafter. Such apparent equilibrium is useful in developing an approach to measuring the number of dopamine transporters present in tissues. Moreover, these results indicate that the utilization of 3&agr; isomers of a variety of 3&bgr;-(substituted phenyl)tropanes will result in greater selectivity for dopamine transporters and a more rapid of achievement of apparent equilibrium.

Growing community of inventors

Cary, NC, United States of America

Philip Abraham