Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2002-12-17
2004-12-28
Ulm, John D. (Department: 1646)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007210, C436S501000
Reexamination Certificate
active
06835548
ABSTRACT:
BACKGROUND OF THE INVENTION
Serotonin is a neuromodulator capable of inducing and modulating a wide variety of behavioral functions such as sleep, appetite, locomotion, sexual activity and vascular contraction. It is accepted that serotonin activity is mediated by its interaction with receptors, designated serotoninergic receptors of 5-HT (for 5-hydroxytryptamine) receptors. Molecular biology studies as well as pharmacological studies have revealed the existence of a large number of subtypes of 5-HT receptors. The 5-HT receptors which have been described to date belong either to the family of receptors associated with ion channels (5-HT3 receptors), or to the family of receptors which interact with G proteins and which possess seven transmembrane domains. Moreover, analysis of the amino acid sequences has shown that the 5-HT receptors which interact with G proteins may be subdivided into six distinct groups: 5-HT1 receptors, comprising the mammalian subtypes 5-HT1a, 5-HT1b, 5-HT1d, 5-HT1e and 5-HT1f, as well as three Drosophila 5-HT receptors; 5-HT2 receptors comprising three subtypes, 5-HT2a, 5-HT2b and 5-HT2c; 5-HT4 receptor; 5-HT5 receptor; 5-HT6 receptor; and 5-HT7 receptor.
Drugs with affinity for 5-HT2 receptors are used to treat schizophrenia, Parkinsonism, and anxiety disorders. The 5-HT2c receptor subtype has been particularly interesting to investigators searching for the molecular bases of neuropsychiatric disorders. The 5-HT2c receptor is widely expressed in the brain where it is involved in regulating endocrine responses. Particular responses include the production and secretion of adrenocorticotropic hormone, oxytocin and prolactin. Genes for mouse, rat and human (Saltzman et al.,
Biochem. Biophys. Res. Commun
. 181:1469, 1991) 5-HT2c receptors have been cloned. Burns et al.,
Nature
vol. 387 15 May 1997 pp. 303-308 describes rat 5-HT2c receptor isoforms resulting from RNA editing events involving transcripts encodong the serotonin receptor. The functional state of 5-HT2c receptors in normal controls and various patient groups has been studied in vivo by administering 1-(3-chlorophenyl)piperazine (mCPP), a non-selective 5-HT2c agonist, and measuring hormonal and psychological responses. In alcoholism, panic disorder, seasonal affective disorder and obsessive-compulsive disorder, mCPP has been shown to induce different hormonal and psychological responses in patients and controls.
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Julius, David, et al., “Molecular Characterization of a Functional cDNA Encoding the Serotonin 1c Receptor,”Science, vol. 241, pp. 558-564, Jul. 29, 1998.
Saltzman, Alan G., et al., “Cloning of the Human Serotonin 5-HT2 and 5-HT1C Receptor Subtypes,”Biochemical and Biophysical Research Comunications, vol., 181, No. 3, pp. 1469-1478, 1991.
Yu, Lei, et al., “The mouse 5-HT1C receptor contains eight hydrophobic domains and is X-linked,”Molecular Brain Research, 11, pp. 143-149, 1991.
Burns, Colleen M., et al., “Regulation of serotonin-2C receptor G-protein coupling by RNA editing,”Nature, vol. 387, pp. 303-308, May 15, 1997.
Julius, David, et al., “The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors,”Neurobiology, 87, pp. 928-932, Feb. 1990.
Fong Tong M.
Liu Jie
Van Der Ploeg Leonardus H.T.
Camara Valerie J.
Merck & Company, Inc.
Parr Richard S.
Ulm John D.
Winokur Melvin
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