Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS3870794 A
Publication typeGrant
Publication dateMar 11, 1975
Filing dateFeb 20, 1974
Priority dateFeb 20, 1974
Publication numberUS 3870794 A, US 3870794A, US-A-3870794, US3870794 A, US3870794A
InventorsEmley Grace S, Hallin Edward R, Hutchinson Ronald R, Murray Nancy J
Original AssigneeFoundation For Behavioral Rese
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Treatment of certain emotional disorders with nicotine compounds
US 3870794 A
Abstract
Nicotine and nicotine derivatives are employed in medicinal treatment routines in a manner which produces unique and beneficial changes in particular emotional disorders. Administration of the compounds causes prompt and discrete reductions of anger, hostility, irritability, and frustration. Simultaneously reactions indicative of fear and anxiety are reduced without general sedation effects. These excessive emotional states are rather supplanted by improved focus upon and performance of necessary tasks. The compounds can be administered in a variety of dosage forms and are effective for the above-described purposes when administered in amounts far less than toxic amounts.
Images(6)
Previous page
Next page
Claims  available in
Description  (OCR text may contain errors)

United States Patent [191 Hutchinson et al.

[ Mar. 11, 1975 TREATMENT OF CERTAIN EMOTIONAL DISORDERS WITH NICOTINE COMPOUNDS [75] Inventors: Ronald R. Hutchinson, Augusta; Grace S. Emley, Ross Township, Kalamazoo County; Edward R. Hallin, Barry Township, Barry County; Nancy J. Murray, Charlestown Township, Kalamazoo County, all of Mich.

[73] Assignee: Foundation for Behavioral Research, Kalamazoo, Mich.

[22] Filed: Feb. 20, 1974 [21] Appl. No.: 444,035

[52] US. Cl. 424/264 [5]] Int. Cl A6ll 27/00 [58] Field of Search 424/264 [56] References Cited UNITED STATES PATENTS 3,048,520 8/1962 McKennis, Jr. et al 424/264 OTHER PUBLICATIONS Merck Index, 7th Ed. (1960), p. 719.

Primary Examiner-Stanley J. Friedman Attorney, Agent, or Firm-Woodhams, Blanchard and Flynn [57] ABSTRACT Nicotine and nicotine derivatives are employed in medicinal treatment routines in a manner which produces unique and beneficial changes in particular emotional disorders. Administration of the compounds causes prompt and discrete reductions of anger, hostility. irritability, and frustration. Simultaneously reactions indicative of fear and anxiety are reduced without general sedation effects. These excessive emotional states are rather supplanted by improved focus upon and performance of necessary tasks. The compounds can be administered in a variety of dosage forms and are effective for the above-described purposes when administered in amounts far less than toxic amounts.

8 Claims, No Drawings TREATMENT OF CERTAIN EMOTIONAL DISORDERS WITH NICOTINE COMPOUNDS BACKGROUND OF THE INVENTION Field of the Invention This invention relates to a new and useful medicinal treatment effective in alleviating emotional states characterized by anger, irritability, tension and concomitant fears and anxieties resulting from stressful or frustrative living conditions. The treatment acts to alter emotional balance and expression by two different processes. Anger, hostility, irritability, frustration, and feelings of tension are reduced but without general response depression, drowsiness, or sedation. Simultaneously, reactions of fear, anxiety, and nervousness are reduced and supplanted by improved focus upon and performance of necessary tasks.

The successful treatment of emotional disorders by chemical means has been hampered historically by the lack of objective laboratory methods for quantitative assessment of specific emotional processes. Previously available tests have relied upon gross visual observations of humans and animals in either natural living settings or special artificial social settings. The variability inherent in such tests contributed greatly to the uncertainty of the findings. During the past decade, precise, objective, and efficient methods have been discovered for the measurement of anger, hostility and aggressivity in both man and animals. The techniques, now well established, allow the simultaneous differential assessment of anger and aggressivity versus fear and anxiety. The efficacy of the medicinal treatment according to this invention has been verified by employing these precise testing methods.

Insofar as we are aware, no prior scientifically based disclosure regarding the benefits of nicotine upon emotional processes, behavioral expression, or performance has occurred. The long standing practice in numerous cultures through many hundreds of years of using tobacco products containing nicotine is well known. Nicotine or nicotine related substances have previously been employed or proposed for employment as a treatment for colic (US. Pat. No. 101,145), tobacco substitute (US. Pat. Nos. 904,521 and 2,981,641), insecticide and parasiticide (US. Pat. No. 2,175,980), muscle relaxant (US. Pat. No. 3,048,520), snake repellent (US. Pat. No. 3,069,314), antihistamine potentiator (US Pat. No. 3,126,319), swine food additive (US. Pat. No. 3,252,802) and skin care agent (U.S. Pat. No. 2,437,561).

SUMMARY OF THE INVENTION This invention is based on the unexpected discovery that the administration of very small quantities of nicotine or nicotine derivatives to mammals, including human beings, produces in the subject treated immediate and substantial reductions in anger or aggressivity and improved task performance, without general response sedation or reduction.

DETAILED DESCRIPTION OF THE INVENTION This invention provides a new and useful medicinal treatment effective in reducing emotional states characterized by anger, irritability, tension and concomitant fears and anxieties resulting from stressful or frustrative living conditions. The treatment acts to alter the emotional balance and expression of the subject treated by two different processes. Anger, hostility, irritability, frustration, and feelings of tension are reduced but without general response depression, drowsiness, or sedation. Simultaneously, reactions of fear, anxiety, and nervousness are reduced and supplanted by improved focus upon and performance of necessary tasks.

Specifically the treatment involves the administration to a mammal, especially human beings, in a pharmaceutically acceptable dosage form, of a therapeutically effective amount of nicotine or its pharmacologically acceptable acid addition salts, especially nicotine tartrate, nicotine bitartrate, nicotine hydrochloride and nicotine sulfate, or a metabolite of nicotine, especially nornicotine or cotinine (available from K & K Laboratories, Plainview, N.Y.). The drug can be administered in any of several forms and dosages suitable to maximum convenience and desired effect. Administration can be (1) oral in the form of powder, capsules, tablet, pill, elixir, syrup, lozenge, or chewable mastic. Representative compositions for oral dosage forms are:

Preparation 1A Capsule Two piece gelatin capsules containing 5 mg of essential active ingredient are prepared as follows:

Nicotine tartrate Lactose U.S.P.

5 mg mg These ingredients are powdered and mixed together and filled into gelatin capsules.

Preparation 1B Syrup A teaspoon (10 cc) of syrup containing 5 mg of essential active ingredient is prepared as follows:

Nicotine tartrate Wild Cherry Syrup 5 mg 10 cc Nicotine tartrate Normal Saline for injection The nicotine tartrate is dissolved in the normal saline for subcutaneous injections. Pharmaceutical preparations can be designed to provide delayed and/or prolonged release of effective agent in accordance with conventional practice. Buffering by conventional pharmaceutical buffering agents can be useful to facilitate drug uptake and minimization of tissue irritation.

Thus, the process of the present invention is accomplished by oral inhalation, insufflation and parenteral administration of pharmaceutical compositions for administration to humans and animals in unit dosage forms, such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, and oral solutions or suspensions containing suitable quantities of nicotine or its pharmacologically acceptable acid addition salts or metabolites.

For oral administration, either solid or fluid unit dosage forms can be prepared. For preparing solid compositions such as tablets, the principal active ingredient is mixed with conventional ingredients such as talc, magnesium stearate, dicalcium phosphate, magnesium aluminum silicate, calcium sulfate, starch, lactose, acacia, methylcellulose, and functionally similar materials as pharmaceutical diluents or carriers. The tablets can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged or delayed action or predetermined successive action of the enclosed medication. For example, the tablet can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permits the inner component to pass intact into the duodenum or to be delayed in release A variety of materials can be used for such enteric layers or coatings such materials including a number of polymeric acids or mixture of polymeric acids with such materials as shellac, cetyl alcohol, cellulose acetate phthalate, styrene maleic acid copolymer and the like. Wafers are prepared in the same manner as tablets, differing only in shape and the inclusion of sucrose or other sweetener and flavor. In their simplest embodiment, capsules, like tablets, are prepared by mixing the compound of the formulation with an inert pharmaceutical diluent and filling the mixture into a hard gelatin capsule of appropriate size. In another embodiment, capsules are prepared by filling hard gelatin capsules with polymeric acid coated beads containing the compound of the formula 1. Soft gelatin capsules are prepared by machine encapsulation of a slurry of the nicotine compound with an acceptable vegetable oil, light liquid petrolatum or other inert oil.

Fluid unit dosage forms for oral administration such as syrups, elixirs, and suspensions can be prepared. The water-soluble forms of the nicotine compounds 1 can be dissolved in an aqueous vehicle together with sugar, aromatic flavoring agents and preservatives to form a syrup. An elixir is prepared by using a hydroalcoholic (ethanol) vehicle with suitable sweeteners such as sucrose together with an aromatic flavoring agent. Suspensions can be prepared of the insoluble forms with a syrup vehicle with the aid of a suspending agent such as acacia, tragacanth, methylcellulose and the like.

For parenteral administration, fluid unit dosage forms are prepared utilizing a nicotine compound and a sterile vehicle, water being preferred. The compound, depending on the form and concentration used, can be either suspended or dissolved in the vehicle. In preparing solutions, a water-soluble form of the nicotine compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampul and sealing. Advantageously, adjuvants such as a local anesthetic, preservative and buffering agents can be dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling into the vial and the water removed under vacuum. The dry lyophilized powder is then sealed in the vial and an accompanying vial of water for injection is supplied to reconstitute the powder prior to use. Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilization cannot be accomplished by filtration. The compound can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle.

The term unit dosage form" as used in the specification and claims refers to physically discrete units suitable as unitary dosages for human subjects and animals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical diluent, carrier or vehicle. The specifications for the novel unit dosage forms of this invention are dictated by and directly dependent on (a) the unique characteristics of the active material and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such an active material for therapeutic use in humans and animals. Examples of suitable unit dosage forms in accord with this invention are tablets, capsules, pills, troches, suppositories, powder packets, granules, wafers, cachets, teaspoonfuls, tablespoonfuls, dropperfuls, ampuls, vials, segregated multiples of any of the foregoing, and other forms as herein described.

Nicotine, its pharmacologically acceptable acid addition salts and metabolites thereof when administered in the dosage amounts specified in this application are not toxic to a normal human adults. The drug is rapidly metabolized by the body to relatively inactive, low toxicity substances and is excreted. Tolerance can develop following repeated usage.

The dosage of the nicotine compound for treatment depends on the route and frequency of administration; the age, weight and condition of the patient; and the severity of the particular emotional condition to be treated. Therapeutically effective dosages appropriate for clinically sufficient results can vary from 0.0002 to 0.2 mg/kg per hour, preferably from 0.005 to 0.05 mg/kg per hour, especially about 0.0125 mg/kg per hour. For continuous (chronic) treatment the nicotine compound can be administered in appropriately sized dosages 3 or 4 times a day so as to supply, in total, the indicated amount of compound per day. For intermittent or occasional treatment, as the need arises, the individual acute dosage (single dosage) needed to promptly produce the described effects will, in most cases for adult humans, lie in the 0.00] 0.10 mg/kg range. Preferred unit dosage forms contain about 0.07 mg/kg for oral administration, 0.02 mg/kg for subcutaneous administration and 0.002 mg/kg for intravenous administration. The initial dosage can suitably be onehalf these amounts and the optimal dose for achieving the desired results can be determined by successive trials of ascending or descending dosage strength.

The duration and periodicity of treatment will necessarily depend upon the nature and chronicity of stressful living conditions. Optimally the drug therapy regimen will be used as an adjunct to other social and psychiatric efforts toward more stress-free living routines.

EXAMPLE 1 Three squirrel monkeys (Saimiri sciureus) served as subjects. In the test apparatus the subjects were partially restrained from the waist down. Painful electric shocks delivered to the tail of the test subject produced subsequent biting attack upon a pneumatic hose suspended in front of the animal (Hutchinson, R. R., et al.,

J. exp. Anal. Behav., 1966, 9, 233-237). Prior to shock 5 delivery the subjects engaged in motor performances of lever pressing and chain pulling (Hutchinson, R.R., et al., J. exp. Anal. Behav., 1971, 15, 141-166). d- Amphetamine in doses from 0.06 0.5 mg/kg increased both responses. Morphine in doses from 0.06

6 EXAMPLE 2 TABLE 2 NlCOTlNE DOSAGE mg/kg/dny .002 .005 .01 .03 .06 l 2 Difference pre-shock +57 +4 +41 +30 -77 35 30 responses from post-shock +53 +3 28 -51 56 3() Controls responses 2.0 mg/kg reduced bothresponses. Administration of nicotine in doses from 0.04 0.8 mg/kg caused a progressive dose dependent reduction in biting attack reactions but left the other motor responses (lever response) substantially unaffected or actually increased. This differential effect of nicotine upon aggression and attack responses, in relation to motor responses is similar to the reported effects of chlorpromazine, a major tranquilizer. The test data is presented in the following table. The data given shows increases and decreases in the number of the indicated responses, in comparison to the responses of the same test subjects tested previously without administration of the compounds (controls). This shows the effect of acute ad- 35 ministration of a single dosage.

TABLE 1 of the dosage range pre-shock responses were elevated or unaffected. This shows the effect of a chronic ad ministration of nicotine over an extended time period.

EXAMPLE 3 Four volunteer adult male human subjects were tested in 30 minute daily sessions in which a repetitive intense pure tone 1 l0 decibel, 3,000 hertz) was delivered for 2 seconds each 3 minutes and their jaw contractions (masseter muscle) were recorded. This loud noise caused jaw clenching immediately after the tone delivery. The values recorded on 2 days prior to nicotine administration are set forth in the column entitled Before Nicotine Administration. On two subsequent days 5 milligrams of nicotine in 5 ounces of water was DOSAGE (mg/kg) d-Amphetnminc .12 .25

Chlorpromazine .06 .5 .06 .12 5 1.0 2.0 Lever Response +5 +12 +30 +60 +20 +25 +50 +5 +10 8 Change Bite Response 25 +1x0 +400 +600 -10 20 100 110 150 150 (hzlngc Morphine Nicotine .00 12 .25 5 1.0 2.0 .04 .16 .32 .64 .11 Lever ponse -7 20 10 50 +5 +10 +5 +20 +8 Change Bite Response 5 -25 35 l00 l l90 -45 +25 75 125 45 Change These effects are statistically significant. administered 15 minutes before the test. All subjects showed marked reductions in jaw contractions produced by the tone while other motor responses were Wilcoxon Signed Ranks Test left unaffected. These values are shown in the column entitled During Nicotine Administration." On the following day, nicotine was not administered and the test was repeated. The values for this test are shown in the column entitled After Nicotine Administration. The data for Average Response Ratio (before/after) is the ratio of jaw contractions occurring in the last twothirds of the intertone interval relative to contractions occurring in the first third of the intertone interval. These effects are statistically significant.

TABLE 3 Before Nicotine During Nicotine After Nicotine Administration Administration Administration Average number of mussetcr contrac- 7.9 2.] 5.5 tions Average contraction force 34 12 29 (uvolls) Average response ratio L? 4.25 2.8 (before/after) EXAMPLE 4 Subsequent to our invention, we reported some of Eleven food deprived albino rats were studied in a test in which they responded on a switch for food. Aperiodically during this test a tone was presented and followed by an electric shock (Estes, W. K. and Skinner, B. F., J. exp. PsychoL, 1941, 29, 390-400). Stabilized performance showed all subjects to be responding for food except during the tone preceding shock. Administration of nicotine in a dosage range from 0.05 0.4 mg/kg produced recovery of responding in this anxiety producing situation during the tone. Responding during other portions of the test was unaffected. This result is similar to the reported effects of chlorpromazine, a major tranquilizer.

TABLE 4 these results in Smoking Behavior; Motives and Incentives, W. L. Dunn (ed.), V. H. Winston (Washington, DC), 1973, 171-195. This article and the references listed therein are incorporated herein by reference, particularly with regard to the significance of our test results.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A method of producing (A) reduction of anger, hostility, irritability, frustration and the behavioral expression of these emotions, without producing general depression, drowsiness or sedation, or (B) reduction of fear, anxiety, nervousness and the behavioral expres- NlCOTlNE DOSAGE (mg/kg) Response increase Suppression Ratio .07 +.l" +.l)4 +.(l4 +.l) -.02 05 Difference from Controls These results are statistically significant. sion of these emotions, with the simultaneous increase 45 in focus upon and performance of necessary tasks, in

EXAMPLE 5 TABLE 5 mammals requiring such treatment, which comprises administering to such a mammal a unit dosage form of a therapeutic composition containing an effective, nontoxic amount of nicotine, pharmaceutically acceptable acid addition salt of nicotine, nornicotine or cotinine, with a pharmaceutically acceptable carrier, diluent or vehicle.

2. A method in accordance with claim I, wherein the mammal is a human and the effective amount is in the range of about 0.0002 mg/kg per hour to about 0.2

NICOTINE DOSAGE (mg/kg) Response lnerense Suppression Ratio Diffel'mn'e from (onliols Wilemon Signed ltnnks 'lest p- .05

mg/kg per hour, administered daily in divided doses.

3. A method in accordance with claim 2, wherein the mammal is a human and the effective amount is in the range of 0.005 mg/kg per hour to 0.05 mg/kg per hour. 4. A method in accordance with claim 1, wherein the mammal is a human and the effective amount is in the range of about 0.001 mg/kg to about 0. ministered in a single dosage.

5. A method according to claim 1 in which said salt 10 mg/kg ad- 10 is selected from the group consisting of nicotine tartrate, nicotine bitartrate, nicotine hydrochloride and nicotine sulfate.

6. A method according to claim 1, in which said com- 4

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3048520 *Jun 6, 1960Aug 7, 1962Medical College Of Virginia FoAntispasmodic
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4574151 *Aug 11, 1983Mar 4, 1986Peter Robin Broughton LawrenceAlkaloids and polysaccharides
US4579858 *Jan 11, 1984Apr 1, 1986Aktiebolaget LeoSmoking substitutes for nasal administration-I
US4655231 *Jan 9, 1984Apr 7, 1987Advanced Tobacco Products, Inc.Snuff and preparation thereof
US4748181 *May 15, 1985May 31, 1988Foundation For Behavioral ResearchMethod for treating hypertension with nicotine
US4806356 *Apr 3, 1987Feb 21, 1989Shaw Alec S WTobacco product
US5004610 *Jun 14, 1990Apr 2, 1991Alza CorporationSubsaturated nicotine transdermal therapeutic system
US5055478 *Jan 21, 1988Oct 8, 1991Cooper Thomas MMethod for stopping smoking
US5077104 *Dec 21, 1989Dec 31, 1991Alza CorporationNicotine packaging materials
US5135753 *Mar 12, 1991Aug 4, 1992Pharmetrix CorporationMethod and therapeutic system for smoking cessation
US5158771 *Nov 21, 1988Oct 27, 1992Spindler Frank RNicotine compositions
US5187169 *Apr 10, 1992Feb 16, 1993R. J. Reynolds Tobacco CompanyMethod for treatment of neurodegenerative diseases
US5212188 *Mar 2, 1992May 18, 1993R. J. Reynolds Tabacco CompanyMethod for treatment of neurodegenerative diseases
US5214060 *Apr 10, 1992May 25, 1993R. J. Reynolds Tobacco CompanyPyridylalkylpiperidine or pyrolidine
US5227385 *Mar 13, 1992Jul 13, 1993Wake Forest UniversityMethod for treatment of neurodegenerative diseases
US5232932 *May 21, 1992Aug 3, 1993R. J. Reynolds Tobacco CompanyMethod for treatment of neurodegenerative diseases
US5232933 *May 21, 1992Aug 3, 1993R. J. Reynolds Tobacco CompanyMethod for treatment of neurodegenerative diseases
US5242916 *Jul 7, 1992Sep 7, 1993R. J. Reynolds Tobacco CompanyMethod for treatment of neurodegenerative diseases
US5242934 *Mar 2, 1992Sep 7, 1993R. J. Reynolds Tobacco CompanyMethod for treatment of neurodegenerative diseases
US5242935 *Mar 6, 1992Sep 7, 1993R. J. Reynolds Tobacco CompanyMethod for treatment of neurodegenerative diseases
US5248690 *Jul 7, 1992Sep 28, 1993R. J. Reynolds Tobacco CompanyMethod for treatment of neurodegenerative diseases
US5268209 *Oct 21, 1991Dec 7, 1993Alza CorporationNicotine packaging materials
US5276043 *Mar 12, 1993Jan 4, 1994R. J. Reynolds Tobacco CompanyAnabasine compounds
US5288872 *Mar 13, 1992Feb 22, 1994Wake Forest UniversityA tropane ring cholinergic agents for alzheimer's, parkinson's diseases
US5326563 *Sep 22, 1992Jul 5, 1994Spindler Frank RNicotine compositions
US5441060 *Feb 8, 1993Aug 15, 1995Duke UniversityDry powder delivery system
US5508038 *Apr 16, 1990Apr 16, 1996Alza CorporationDrug delivery patches having mixture of high and low molecular weight polymers as adhesives which dissolve active agents, free of plasticizers and tackifiers
US5525351 *Dec 20, 1993Jun 11, 1996Dam; AndersNicotine containing stimulant unit
US5573774 *Jun 6, 1995Nov 12, 1996Keenan; Robert M.Nicotine metabolites, nicotine dependence and human body weight
US5583140 *May 17, 1995Dec 10, 1996Bencherif; MerouaneAdministering 2-azabicyclo(2.2.2)oct-5-ene derivatives to treat neurodegenerative disorders such as senile dementia of alzheimer's type
US5596007 *May 18, 1992Jan 21, 1997Pharmaco Behavioral Associates, Inc.Lessening withdrawal syndrome for tobacco and nicotine
US5612357 *Aug 22, 1994Mar 18, 1997Pharmaco Behavioral Associates, Inc.Use of cotinine to assist in the cessation of tobacco smoking
US5633008 *Aug 12, 1993May 27, 1997Osborne; James L.Method of administering nicotine transdermally
US5643928 *Oct 21, 1992Jul 1, 1997Pharmaco Behavioral Associates, Inc.Human body weight management
US5731314 *Jan 6, 1995Mar 24, 1998Bencherif; MerouaneAdministering aryl substituted olefinic amine compounds or aryl substituted acetylenic amine compounds to a patient
US5733574 *Jun 7, 1995Mar 31, 1998Dam; AndersNicotine containing stimulant unit
US5747512 *Aug 1, 1996May 5, 1998Pharmaco Behavioral Associates, Inc.Use of cotinine to alleviate tobacco withdrawal syndrome
US5776956 *Jul 30, 1996Jul 7, 1998Lectec CorporationUse of cotinine in treating psychiatric disorders
US5824692 *Jan 6, 1995Oct 20, 1998Lippiello; Patrick MichaelPharmaceutical compositions for prevention and treatment of central nervous system disorders
US5869503 *May 2, 1994Feb 9, 1999Keenan; Robert M.Nicotine metabolites and human body weight
US5869505 *Feb 2, 1993Feb 9, 1999Keenan; Robert M.Nicotine metabolites and nicotine dependence
US5880164 *Oct 3, 1996Mar 9, 1999Lectec CorporationNontoxic vegetable material coated with cotinine; smoking cessation or maintaining abstinence
US5885998 *Feb 12, 1998Mar 23, 1999Bencherif; MerouaneAdministering an effective amount of an aryl subsistituted aliphatic compound, an aryl substituted olefinic amine compound or an aryl substituted acetylenic compound such as 4-(5-pyrimidinyl)-3-butene-1-amine
US5889029 *Nov 13, 1997Mar 30, 1999Lectec CorporationUse of cotinine in treating psychiatric disorders
US5922723 *Sep 5, 1996Jul 13, 1999Bencherif; MerouaneAdministering to the patient suffering with central nervous system disorder a 2-azabicyclo(2,2,1)hept-5-ene derivative
US5972974 *Nov 7, 1996Oct 26, 1999Pharmaco Behavioral Associates, Inc.Transdermal nicotine metabolites and human body weight
US6024097 *Apr 3, 1998Feb 15, 2000J Mom TrustProduct for assisting a smoker in giving up the habit
US6100269 *May 6, 1999Aug 8, 2000Bencherif; MerouanePharmaceutical compositions for prevention and treatment of central nervous system disorders
US6102036 *Jul 30, 1998Aug 15, 2000Smoke-StopBreath activated inhaler
US6107298 *Mar 12, 1999Aug 22, 2000Bencherif; MerouaneMethods for prevention and treatment of Tourette's syndrome and schizophrenia
US6110495 *Nov 17, 1997Aug 29, 2000Dam; AndersA controlled release of nicotine and flavor additives from a smokeless nicotine stimulation can be obtained by a saliva soluble stimulant comprising a gel formed by gelation of water binding gel, nicotine or other alkaloids
US6165497 *Mar 1, 1991Dec 26, 2000Alza CorporationSubsaturated nicotine transdermal therapeutic system
US6350479Jun 4, 1999Feb 26, 2002Regent Court TechnologiesTreating depression with alcohol extracts of tobacco
US6569470Jan 11, 2002May 27, 2003Regent Court Technologies, LlcMonoamine oxidase (MAO) inhibitors and uses thereof
US6929811Mar 26, 2003Aug 16, 2005Regent Court Technologies, LlcActive agent is selected from the group consisting of anabasine, anatabine, nomicotine, Yerbamate (Ilex paraguariensis) extract, and a liquid extract of tobacco; especially for treating psychological disorders
USRE39588Oct 31, 1990Apr 24, 2007Alza CorporationDelays onset of drug administration; does not deliver an initial burst of drug, less likely to cause irritation; stabilizes an active drug by storing it within a transdermal therapeutic system, in form suitable for storage
DE3645036A1 *Nov 18, 1986Jan 5, 1989Forschungsgesellschaft RauchenNicotine-containing composition
EP1073466A1 *Apr 21, 1999Feb 7, 2001Duke UniversitySolution containing nicotine
WO1989004661A1 *Nov 21, 1988Jun 1, 1989Indaus International Pty LtdNicotine compositions
WO1993023045A1 *May 17, 1993Nov 25, 1993Dorothy K HatsukamiUse of cotinine to alleviate tobacco withdrawal syndrome
WO1999062531A1 *Jun 4, 1999Dec 9, 1999Regent Court TechnologiesMonoamine oxidase (mao) inhibitors and uses thereof
WO2003049559A2 *Dec 10, 2002Jun 19, 2003Marshall A ThompsonMethod of producing a nicotine composition
WO2006004418A2 *Jun 27, 2005Jan 12, 2006Erik LaabakkEncapsulated tobacco smoke
Classifications
U.S. Classification514/343
International ClassificationA61K31/465
Cooperative ClassificationA61K31/465
European ClassificationA61K31/465