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Publication numberUS3624215 A
Publication typeGrant
Publication dateNov 30, 1971
Filing dateJun 25, 1970
Priority dateJun 25, 1970
Publication numberUS 3624215 A, US 3624215A, US-A-3624215, US3624215 A, US3624215A
InventorsElizabeth Goodsell, Herman Hal Stein
Original AssigneeAbbott Lab
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
8-substituted theophyllines as anti-anxiety agents
US 3624215 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

United States Patent [7 2] Inventors Herman Hal Stein Skokie; Elizabeth Goodsell, Waukegan, both of III. [21] Appl. No. 49,921 [22] Filed June 25, 1970 [45] Patented Nov. 30, 1971 [7 3 1 Assignee Abbott Laboratories North Chicago, Ill.

[54] S-SUBSTITUTED THEOPHYLLINES AS ANTI- ANXIETY AGENTS 4 Claims, No Drawings s21 u.s.c| 424/253 OTHER REFERENCES Quevauviller, Actualitis PharmacoL, 8: 106- 52 1955).

Primary ExaminerStanley .l. Freidman Attorney-Robert L. Niblack ABSTRACT: A method of alleviating anxiety in mammals exhibiting such symptoms by administering from I to 50 mg./kg. daily of an 8-substituted theophylline.

S-SUBSTITUTED TI-IEOPHYLLINES AS ANTI-ANXIETY AGENTS DETAILED DESCRIPTION OF THE INVENTION This invention relates to a method of relieving anxiety in patients in order to restore such patients to a more normal and thus contribute to their physical and mental well being.

Patients suffering from depression manifest one or more of a variety of symptoms. Generally speaking, depressed patients feel incapable of dealing with their responsibilities; they lose interest in their jobs, families and hobbies. The predominant symptoms of depression are hypochondria, anorexia, insomnia, anergia, anhedonia and pessimism. However, some patients suffering from depression are also anxious and nervous. In treating such patients, it is desirable to have a therapeutic agent which has tranquilizing or sedative overtones. The present invention provides a method of treating anxious or depressed patients employing compounds which exhibit antidepressant and sedative properties. Accordingly, for the purpose of this disclosure, the ii-substituted theophyllines used herein shall he referred to as nntianxiety agents.

Theophyllinc and a number of its derivatives have been reported to possess activity as central nervous system stimulants and as diuretics. (Quevauviller, Actualitis Pharmacol. 8: 106-52 (I955). We have'unexpectedly found that certain 8- substituted theophyllines possess activity as sedative antidepressants. Thus, the compounds are generally useful in treating patients who are suffering from anxiety or manifesting other symptoms of depression.

The compounds useful in the practice of this invention are 8-substituted theophyllines represented by the formula wherein R is C C alkyl or C -C cycloalkyl.

The term alkyl, as used herein, refers to both straight and branched chain alkyl such as methyl, ethyl, n-propyl, isopropyl, nbutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl and the like.

The antidepressant activity of the above compounds was established using the modified DOPA test described by Everett et al., Fed. Proc., 23, 198(1964).

In the practice of this invention, the compounds are administered to patients exhibiting the symptoms of depression, including anxiety, particularly in patients in need of sedation, in dosages of from 1 to 50 mg./kg. of body weight daily, either in single or divided doses. While the compounds exhibit both oral and parenteral activity, the preferred route of administration is the oral route.

The compounds of the present invention for use as antidepressant or antianxiety agents can be incorporated in to various pharmaceutically acceptable dosage forms such as tablets, capsules, pills, suspensions and the like, for immediate or sustained release, by combining them with suitable carriers or diluents according to methods well known in the art. In addition to active agent and the carrier or diluent, the dosage forms may include various excipients, binders, fillers, flavoring and sweetening agents, and the like, necessary in the formulation of the desired pharmaceutical preparation. However, in the case of filled capsules, for example, the antianxiety agent can be the sole ingredient.

Illustrative compounds useful in the practice of this invention are:

B-n-Pentyl-theophylline S-Cyclopentyl-theophylline 8-n-Hexyl-theophylline 8 n-Butyl-theophylline 8-iso-Butyl-theophylline ll-Cyclopropyl-theophyllinc 8-n-Heptyl-theophylline The B-substituted theophyllines employed in the practice of 5 this invention were prepared according to the methods described by Hager et al., J.Am. Pharm. Assoc., 43, I52 (I954) and by first et al., J. Chem Ber., 93, 99 (I960). Generally speaking, the active agents can be prepared by reacting 5,6-diamino-l,B-dimethyluracil (commercially available from Aldrich Chemical Company, Milwaukee, Wis.)

O l with an acid of the formula wherein R is C C, alkyl or C -C cycloalkyl. The synthesis is represented by the following reaction sequence.

HgC-N N A The following example further illustrates the present invention.

EXAMPLE 1 marked activity. The results are summarized in table I.

TABLE I Compound Dosage (mg/kg.) Modified DOPA Test Response Elavil 30 2+ il-n-Propyl theophylline 30 3+ B-Cyclopropyl theophylline 30 4+ 8-Cyclopentyl theophylline 30 3+ wherein R is C C, alkyl, or C -C cycloalkyl. cyciogr opyl theophylline. 2. The method of claim 1 wherein the compound is 8-n- 4. The method of claim 1 wherein the compound is 8- propyl theophylline. cxciopentyl theophylline.

3. The method of claim 1 wherein the compound is 8-

Non-Patent Citations
1 *Quevauviller, Actualitis Pharmacol., 8:106 52 (1955).
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4089959 *Mar 31, 1976May 16, 1978Cooper Laboratories, Inc.Long-acting xanthine bronchodilators and antiallergy agents
US4755517 *Jul 31, 1986Jul 5, 1988Warner-Lambert CompanyDerivatives of xanthine, pharmaceutical compositions and methods of use therefor
US4772607 *Jul 14, 1986Sep 20, 1988Warner-Lambert CompanyAlzheimer*s disease, cns stimulant, antifibrillatory, bronchodilator
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US5861405 *Nov 7, 1994Jan 19, 1999The United States Of America As Represented By The Department Of Health And Human ServicesA2-selective adenosine receptor antagonist as antidepressants and cns stimulants
US8871751Jan 19, 2009Oct 28, 2014The Board Of Trustees Of The University Of IllinoisCompositions and methods relating to nuclear hormone and steroid hormone receptors including inhibitors of estrogen receptor alpha-mediated gene expression and inhibition of breast cancer
EP0374808A2 *Dec 18, 1989Jun 27, 1990Boehringer Ingelheim KgXanthin derivatives having an adenosin-antagonist activity
EP0590919A1 *Sep 28, 1993Apr 6, 1994Kyowa Hakko Kogyo Co., Ltd.Therapeutic agents for parkinson's disease
WO1992000297A1 *Jun 19, 1991Jan 9, 1992Boehringer Ingelheim IntNew xanthine derivatives
U.S. Classification514/263.34, 544/267
International ClassificationC07D473/08
Cooperative ClassificationC07D473/08
European ClassificationC07D473/08