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

The Government of the United States of America, As Represented by the

Markku I Linnoila

David Goldman

Michael J Durcan

Matti Virkkunen

Richard G Lister

Kenneth Alan Jacobson

Kenneth L Kirk

Markku Koulu

Ullamari Pesonen

Kazunori Mine

Thomas Miller

David A Nielsen

Jaakko Lappalainen

An allelic variant of the 5HT7 serotonin receptor was discovered. Family study data indicate that this variant can be correlated to alchoholic offerders. DNA encoding the variant protein, the protein itself, vectors containing the variant gene and cell lines carrying a vector with the variant gene are part of the invention.

Allelic variation of the serotonin 5HT7 receptor

We describe identification of a non-conservative amino acid substitution in the 5-HT.sub.2C receptor gene. The variant was found using single strand conformational polymorphism (SSCP) analysis. By typing this polymorphism in CEPH families, the gene was genetically mapped on the long arm of the X chromosome. Since this polymorphism was not detectable as a conventional RFLP, we also developed a PCR-RFLP based method which allows rapid genotyping in populations and families.

Allelic variation of the serotonin 5HT.sub.2c receptor

A method of detecting abnormal serotonergic function in an impulsive human subject is disclosed. The method comprises detecting an L allele of a gene encoding tryptophan hydroxylase. The invention also includes an isolated nucleic acid having a sequence specific to an L allele of a gene encoding tryptophan hydroxylase. The nucleic acid may migrate in a denaturing gel at the same rate as a second nucleic acid specific to a corresponding region of a U allele of a gene encoding tryptophan hydroxylase, and migrate in a nondenaturing gel at a rate about 1.02 times the migration rate of the second nucleic acid.

Method for detecting abnormal serotonergic function

A method is provided for attenuating the intoxicating effects of ethyl alcohol in a patient, by administering to a patient in need thereof, an alpha-2 adrenoceptor antagonist compound. Two preferred compounds useful in the present invention, each being a highly potent and selective alpha-2 adrenoceptor antagonist, are atipamezole and idazoxan.

Attenuation of ethyl alcohol intoxication with alpha-2 adrenoceptor

Primary and secondary amines in biological fluids are selectively derivitized by reaction with esters of N-hydroxysuccinimide or N-hydroxysulfosuccinimide to form an N-acylated derivative. Those N-acylated derivatives may then be extracted into a polar organic phase and extracted. Non-electroactive amines may be made suitable for coulometric analysis by selecting the ester used so as to attach an electroactive group to the amine. For example, histamine may be reacted with the Bolton-Hunter reagent to form a suitable derivative in high yield.

Derivatization of amines for electrochemical detection

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Bethesda, MD, United States of America

Markku I Linnoila