Oregon Health & Science University

State of Oregon

Mark Sonders

Eckard Weber

John F Keana

David K Grandy

James R Bunzow

The present invention relates to novel mammalian biogenic amine receptor proteins and genes that encode such proteins. The invention is directed toward the isolation and characterization of mammalian trace amine receptor proteins. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to rat and human homologues of a mammalian trace amine receptor gene. Also provided are recombinant expression constructs capable of expressing the mammalian trace amine receptor genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the mammalian trace amine receptor proteins encoded therein. The invention also provides methods for screening compounds in vitro that are capable of binding to the mammalian trace amine receptor proteins of the invention, and further characterizing the binding properties of such compounds and functional consequences thereof in comparison with known trace amine receptor agonists and antagonists. Improved methods of pharmacological screening are provided thereby.

Nucleic acids encoding a biogenic amine receptor

1,3-Disubstituted-guanidines, e.g., of the formula ##STR1## wherein R and R' are hydrocarbon groups which preferably are the same, e.g., 1,3-dibutyl-guanidine, 1,3-diphenyl-guanidine and 1,3-di-o-tolyl-guanidine, are highly selective ligands for sigma brain receptors and are useful in the diagnosis and treatment of hallucination associated psychotic mental illness and chronic mental depression. Tritium labeled 1,3-di-(o-tolyl)-guanidine is useful as a screening tool for compounds having selective sigma receptor binding activity, as it is displaced from isolated mammalian brain membrane to which it is bound portionately to the activity of such a compound.

Growing community of inventors

Portland, OR, United States of America

Mark Sonders