New! View global litigation for patent families

US3870794A - Treatment of certain emotional disorders with nicotine compounds - Google Patents

Treatment of certain emotional disorders with nicotine compounds Download PDF

Info

Publication number
US3870794A
US3870794A US44403574A US3870794A US 3870794 A US3870794 A US 3870794A US 44403574 A US44403574 A US 44403574A US 3870794 A US3870794 A US 3870794A
Authority
US
Grant status
Grant
Patent type
Prior art keywords
nicotine
dosage
mg
kg
administration
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
Inventor
Ronald R Hutchinson
Grace S Emley
Edward R Hallin
Nancy J Murray
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Foundation for Behavioral Research
Original Assignee
Foundation for Behavioral Research
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465Nicotine; Derivatives thereof

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 abovedescribed purposes when administered in amounts far less than toxic amounts.

Description

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

Claims (8)

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 EXPRESSION OF THESE EMOTIONS, WITH THE SIMULTANEOUS INCREASE IN FOCUS UPON AND PERFORMANCE OF NECESSARY TASKS, IN MAMMALS REQUIRING SUCH TREATMENT, WHICH COMPRISES ADMINISTERING TO SUCH A MAMMAL A UNIT DOSAGE FORM OF A THERAPEUTIC COMPOSITION CONTAINING AN EFFECTIVE, NON-TOXIC AMOUNT OF NICOTINE, PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALT OF NICOTINE, NORNICOTINE OR COTININE, WITH A PHARMACEUTICALLY ACCEPTABLE CARRIER, DILUENT OR VEHICLE.
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 expression of these emotions, with the simultaneous increase in focus upon and performance of necessary tasks, in mammals requiring such treatment, which comprises administering to such a mammal a unit dosage form of a therapeutic composition containing an effective, non-toxic 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 1, 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 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 0.10 mg/kg administered in a single dosage.
5. A method according to claim 1 in which said salt 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 composition is administered orally.
7. A method according to claim 1, in which said composition is administered parenterally.
US3870794A 1974-02-20 1974-02-20 Treatment of certain emotional disorders with nicotine compounds Expired - Lifetime US3870794A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US3870794A US3870794A (en) 1974-02-20 1974-02-20 Treatment of certain emotional disorders with nicotine compounds

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US3870794A US3870794A (en) 1974-02-20 1974-02-20 Treatment of certain emotional disorders with nicotine compounds

Publications (1)

Publication Number Publication Date
US3870794A true US3870794A (en) 1975-03-11

Family

ID=23763223

Family Applications (1)

Application Number Title Priority Date Filing Date
US3870794A Expired - Lifetime US3870794A (en) 1974-02-20 1974-02-20 Treatment of certain emotional disorders with nicotine compounds

Country Status (1)

Country Link
US (1) US3870794A (en)

Cited By (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4574151A (en) * 1982-08-20 1986-03-04 Peter Robin Broughton Lawrence Amine salts and products containing them
US4579858A (en) * 1983-01-21 1986-04-01 Aktiebolaget Leo Smoking substitutes for nasal administration-I
US4655231A (en) * 1984-01-09 1987-04-07 Advanced Tobacco Products, Inc. Snuff and preparation thereof
FR2602974A1 (en) * 1985-03-05 1988-02-26 Ciba Geigy Ag A pharmaceutical composition comprising nicotine or its derivatives
US4748181A (en) * 1979-08-28 1988-05-31 Foundation For Behavioral Research Method for treating hypertension with nicotine
DE3645036A1 (en) * 1986-11-18 1989-01-05 Forschungsgesellschaft Rauchen Nicotine-containing composition
US4806356A (en) * 1983-06-29 1989-02-21 Shaw Alec S W Tobacco product
WO1989004661A1 (en) * 1987-11-19 1989-06-01 Indaus International Pty Ltd Nicotine compositions
US5004610A (en) * 1988-06-14 1991-04-02 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US5055478A (en) * 1986-06-19 1991-10-08 Cooper Thomas M Method for stopping smoking
US5077104A (en) * 1989-12-21 1991-12-31 Alza Corporation Nicotine packaging materials
US5135753A (en) * 1991-03-12 1992-08-04 Pharmetrix Corporation Method and therapeutic system for smoking cessation
US5187169A (en) * 1992-04-10 1993-02-16 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5212188A (en) * 1992-03-02 1993-05-18 R. J. Reynolds Tabacco Company Method for treatment of neurodegenerative diseases
US5214060A (en) * 1992-04-10 1993-05-25 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5227385A (en) * 1992-03-13 1993-07-13 Wake Forest University Method for treatment of neurodegenerative diseases
US5232932A (en) * 1992-05-21 1993-08-03 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5232933A (en) * 1992-05-21 1993-08-03 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5242916A (en) * 1992-07-07 1993-09-07 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5242935A (en) * 1992-03-06 1993-09-07 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5242934A (en) * 1992-03-02 1993-09-07 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5248690A (en) * 1992-07-07 1993-09-28 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
WO1993023045A1 (en) * 1992-05-18 1993-11-25 Pharmaco Behavioral Associates, Inc. Use of cotinine to alleviate tobacco withdrawal syndrome
US5276043A (en) * 1992-04-10 1994-01-04 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5288872A (en) * 1992-03-13 1994-02-22 Wake Forest University Compounds for treatment of neurodegenerative diseases
US5441060A (en) * 1993-02-08 1995-08-15 Duke University Dry powder delivery system
US5508038A (en) * 1990-04-16 1996-04-16 Alza Corporation Polyisobutylene adhesives for transdermal devices
US5525351A (en) * 1989-11-07 1996-06-11 Dam; Anders Nicotine containing stimulant unit
US5573774A (en) * 1993-02-02 1996-11-12 Keenan; Robert M. Nicotine metabolites, nicotine dependence and human body weight
US5583140A (en) * 1995-05-17 1996-12-10 Bencherif; Merouane Pharmaceutical compositions for the treatment of central nervous system disorders
US5596007A (en) * 1992-05-18 1997-01-21 Pharmaco Behavioral Associates, Inc. Therapeutic method to alleviate the craving associated with cessation of tobacco with cotinine
US5612357A (en) * 1992-05-18 1997-03-18 Pharmaco Behavioral Associates, Inc. Use of cotinine to assist in the cessation of tobacco smoking
US5643928A (en) * 1992-10-21 1997-07-01 Pharmaco Behavioral Associates, Inc. Human body weight management
US5731314A (en) * 1995-01-06 1998-03-24 Bencherif; Merouane Pharamceutical compositions for prevention and treatment of tourette's syndrome
US5776956A (en) * 1996-07-30 1998-07-07 Lectec Corporation Use of cotinine in treating psychiatric disorders
US5824692A (en) * 1995-01-06 1998-10-20 Lippiello; Patrick Michael Pharmaceutical compositions for prevention and treatment of central nervous system disorders
US5869505A (en) * 1993-02-02 1999-02-09 Keenan; Robert M. Nicotine metabolites and nicotine dependence
US5880164A (en) * 1995-03-06 1999-03-09 Lectec Corporation Nicotine-free smoking material
WO1999062531A1 (en) * 1998-06-05 1999-12-09 Regent Court Technologies Monoamine oxidase (mao) inhibitors and uses thereof
US6024097A (en) * 1992-02-20 2000-02-15 J Mom Trust Product for assisting a smoker in giving up the habit
US6102036A (en) * 1994-04-12 2000-08-15 Smoke-Stop Breath activated inhaler
EP1073466A1 (en) * 1998-04-30 2001-02-07 Duke University Solution containing nicotine
US20030108592A1 (en) * 2001-12-10 2003-06-12 Thompson Marshall Anlauf Method of producing a nicotine composition
US20050131031A1 (en) * 2001-12-10 2005-06-16 Thompson Marshall A. Method of producing a nicotine composition
WO2006004418A2 (en) * 2004-07-05 2006-01-12 Laabakk Erik Encapsulated tobacco smoke
US20060204598A1 (en) * 2001-12-10 2006-09-14 Thompson Marshall A Nicotine-alternative compositions and methods of producing such compositions
USRE39588E1 (en) 1987-11-09 2007-04-24 Alza Corporation Transdermal drug delivery device
US20100092616A1 (en) * 2005-01-27 2010-04-15 Marshall Anlauf Thompson Method of producing a nicotine composition
US20100104504A1 (en) * 2008-09-24 2010-04-29 University Of South Florida Materials and methods for diagnosis, prevention and/or treatment of stress disorders and conditions associated with abeta peptide aggregation
US20100160376A1 (en) * 2001-12-10 2010-06-24 Marshall Anlauf Thompson Nicotine-alternative compositions and methods of producing such compositions

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3048520A (en) * 1960-06-06 1962-08-07 Medical College Of Virginia Fo Antispasmodic

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3048520A (en) * 1960-06-06 1962-08-07 Medical College Of Virginia Fo Antispasmodic

Cited By (76)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4748181A (en) * 1979-08-28 1988-05-31 Foundation For Behavioral Research Method for treating hypertension with nicotine
US4574151A (en) * 1982-08-20 1986-03-04 Peter Robin Broughton Lawrence Amine salts and products containing them
US4579858A (en) * 1983-01-21 1986-04-01 Aktiebolaget Leo Smoking substitutes for nasal administration-I
US4806356A (en) * 1983-06-29 1989-02-21 Shaw Alec S W Tobacco product
US4655231A (en) * 1984-01-09 1987-04-07 Advanced Tobacco Products, Inc. Snuff and preparation thereof
FR2602974A1 (en) * 1985-03-05 1988-02-26 Ciba Geigy Ag A pharmaceutical composition comprising nicotine or its derivatives
US5055478A (en) * 1986-06-19 1991-10-08 Cooper Thomas M Method for stopping smoking
DE3645036A1 (en) * 1986-11-18 1989-01-05 Forschungsgesellschaft Rauchen Nicotine-containing composition
USRE39588E1 (en) 1987-11-09 2007-04-24 Alza Corporation Transdermal drug delivery device
WO1989004661A1 (en) * 1987-11-19 1989-06-01 Indaus International Pty Ltd Nicotine compositions
US5326563A (en) * 1987-11-19 1994-07-05 Spindler Frank R Nicotine compositions
US5158771A (en) * 1987-11-19 1992-10-27 Spindler Frank R Nicotine compositions
US5004610A (en) * 1988-06-14 1991-04-02 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US6165497A (en) * 1988-06-14 2000-12-26 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US5633008A (en) * 1988-06-14 1997-05-27 Osborne; James L. Method of administering nicotine transdermally
US5733574A (en) * 1989-11-07 1998-03-31 Dam; Anders Nicotine containing stimulant unit
US6110495A (en) * 1989-11-07 2000-08-29 Dam; Anders Nicotine containing stimulant unit
US5525351A (en) * 1989-11-07 1996-06-11 Dam; Anders Nicotine containing stimulant unit
US5077104A (en) * 1989-12-21 1991-12-31 Alza Corporation Nicotine packaging materials
US5268209A (en) * 1989-12-21 1993-12-07 Alza Corporation Nicotine packaging materials
US5508038A (en) * 1990-04-16 1996-04-16 Alza Corporation Polyisobutylene adhesives for transdermal devices
US5135753A (en) * 1991-03-12 1992-08-04 Pharmetrix Corporation Method and therapeutic system for smoking cessation
US6024097A (en) * 1992-02-20 2000-02-15 J Mom Trust Product for assisting a smoker in giving up the habit
US5212188A (en) * 1992-03-02 1993-05-18 R. J. Reynolds Tabacco Company Method for treatment of neurodegenerative diseases
US5242934A (en) * 1992-03-02 1993-09-07 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5242935A (en) * 1992-03-06 1993-09-07 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5227385A (en) * 1992-03-13 1993-07-13 Wake Forest University Method for treatment of neurodegenerative diseases
US5288872A (en) * 1992-03-13 1994-02-22 Wake Forest University Compounds for treatment of neurodegenerative diseases
US5276043A (en) * 1992-04-10 1994-01-04 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5214060A (en) * 1992-04-10 1993-05-25 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5187169A (en) * 1992-04-10 1993-02-16 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
WO1993023045A1 (en) * 1992-05-18 1993-11-25 Pharmaco Behavioral Associates, Inc. Use of cotinine to alleviate tobacco withdrawal syndrome
US5747512A (en) * 1992-05-18 1998-05-05 Pharmaco Behavioral Associates, Inc. Use of cotinine to alleviate tobacco withdrawal syndrome
US5612357A (en) * 1992-05-18 1997-03-18 Pharmaco Behavioral Associates, Inc. Use of cotinine to assist in the cessation of tobacco smoking
US5596007A (en) * 1992-05-18 1997-01-21 Pharmaco Behavioral Associates, Inc. Therapeutic method to alleviate the craving associated with cessation of tobacco with cotinine
US5232932A (en) * 1992-05-21 1993-08-03 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5232933A (en) * 1992-05-21 1993-08-03 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5242916A (en) * 1992-07-07 1993-09-07 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5248690A (en) * 1992-07-07 1993-09-28 R. J. Reynolds Tobacco Company Method for treatment of neurodegenerative diseases
US5643928A (en) * 1992-10-21 1997-07-01 Pharmaco Behavioral Associates, Inc. Human body weight management
US5573774A (en) * 1993-02-02 1996-11-12 Keenan; Robert M. Nicotine metabolites, nicotine dependence and human body weight
US5972974A (en) * 1993-02-02 1999-10-26 Pharmaco Behavioral Associates, Inc. Transdermal nicotine metabolites and human body weight
US5869503A (en) * 1993-02-02 1999-02-09 Keenan; Robert M. Nicotine metabolites and human body weight
US5869505A (en) * 1993-02-02 1999-02-09 Keenan; Robert M. Nicotine metabolites and nicotine dependence
US5441060A (en) * 1993-02-08 1995-08-15 Duke University Dry powder delivery system
US6102036A (en) * 1994-04-12 2000-08-15 Smoke-Stop Breath activated inhaler
US5885998A (en) * 1995-01-06 1999-03-23 Bencherif; Merouane Methods for prevention and treatment of attention deficit disorder
US6107298A (en) * 1995-01-06 2000-08-22 Bencherif; Merouane Methods for prevention and treatment of Tourette's syndrome and schizophrenia
US5824692A (en) * 1995-01-06 1998-10-20 Lippiello; Patrick Michael Pharmaceutical compositions for prevention and treatment of central nervous system disorders
US5731314A (en) * 1995-01-06 1998-03-24 Bencherif; Merouane Pharamceutical compositions for prevention and treatment of tourette's syndrome
US5880164A (en) * 1995-03-06 1999-03-09 Lectec Corporation Nicotine-free smoking material
US6100269A (en) * 1995-05-17 2000-08-08 Bencherif; Merouane Pharmaceutical compositions for prevention and treatment of central nervous system disorders
US5922723A (en) * 1995-05-17 1999-07-13 Bencherif; Merouane Pharmaceutical compositions for prevention and treatment of central nervous system disorders
US5583140A (en) * 1995-05-17 1996-12-10 Bencherif; Merouane Pharmaceutical compositions for the treatment of central nervous system disorders
US5776956A (en) * 1996-07-30 1998-07-07 Lectec Corporation Use of cotinine in treating psychiatric disorders
US5889029A (en) * 1996-07-30 1999-03-30 Lectec Corporation Use of cotinine in treating psychiatric disorders
EP1073466A1 (en) * 1998-04-30 2001-02-07 Duke University Solution containing nicotine
JP2002512978A (en) * 1998-04-30 2002-05-08 デューク ユニバーシティ Nicotine-containing solution
EP1073466A4 (en) * 1998-04-30 2001-08-16 Univ Duke Solution containing nicotine
US6350479B1 (en) 1998-06-05 2002-02-26 Regent Court Technologies Treating depression with alcohol extracts of tobacco
WO1999062531A1 (en) * 1998-06-05 1999-12-09 Regent Court Technologies Monoamine oxidase (mao) inhibitors and uses thereof
US20050176777A1 (en) * 1998-06-05 2005-08-11 Regent Court Technologies Monoamine oxidase (MAO) inhibitors and uses thereof
US6929811B2 (en) 1998-06-05 2005-08-16 Regent Court Technologies, Llc Monoamine oxidase (MAO) inhibitors and uses thereof
US20030185908A1 (en) * 1998-06-05 2003-10-02 Regent Court Technologies Monoamine oxidase (MAO) inhibitors and uses thereof
US6569470B2 (en) 1998-06-05 2003-05-27 Regent Court Technologies, Llc Monoamine oxidase (MAO) inhibitors and uses thereof
US20050131031A1 (en) * 2001-12-10 2005-06-16 Thompson Marshall A. Method of producing a nicotine composition
WO2003049559A3 (en) * 2001-12-10 2003-08-14 Marshall A Thompson Method of producing a nicotine composition
WO2003049559A2 (en) * 2001-12-10 2003-06-19 Thompson Marshall A Method of producing a nicotine composition
US20100160376A1 (en) * 2001-12-10 2010-06-24 Marshall Anlauf Thompson Nicotine-alternative compositions and methods of producing such compositions
US20030108592A1 (en) * 2001-12-10 2003-06-12 Thompson Marshall Anlauf Method of producing a nicotine composition
US20060204598A1 (en) * 2001-12-10 2006-09-14 Thompson Marshall A Nicotine-alternative compositions and methods of producing such compositions
WO2006004418A3 (en) * 2004-07-05 2006-10-05 Erik Laabakk Encapsulated tobacco smoke
WO2006004418A2 (en) * 2004-07-05 2006-01-12 Laabakk Erik Encapsulated tobacco smoke
US20100092616A1 (en) * 2005-01-27 2010-04-15 Marshall Anlauf Thompson Method of producing a nicotine composition
US9801865B2 (en) * 2008-09-24 2017-10-31 The United States Of America As Represented By The Department Of Veteran Affairs Materials and methods for diagnosis, prevention and/or treatment of stress disorders and conditions associated with abeta peptide aggregation
US20100104504A1 (en) * 2008-09-24 2010-04-29 University Of South Florida Materials and methods for diagnosis, prevention and/or treatment of stress disorders and conditions associated with abeta peptide aggregation

Similar Documents

Publication Publication Date Title
US3679798A (en) Composition comprising arylaminooxazoline and antichloligeneric agent
US4876092A (en) Sheet-shaped adhesive preparation applicable to oral cavity
US6376550B1 (en) Pharmaceutical compositions containing tramadol for migraine
Swan et al. Protection by NMDA antagonists against selective cell loss following transient ischaemia
US5362756A (en) Use of fedotozine in the treatment of functional states of intestinal obstructions
US5719185A (en) Use for GABA agonists for treating emesis
US3879555A (en) Method of treating drug addicts
US3784684A (en) Coronary dilator in a pharmaceutical dosage unit form
US20050038062A1 (en) Methods and materials for the treatment of pain comprising opioid antagonists
US3983234A (en) Treatment of dyskinesias
US4690927A (en) Pharmaceutical compositions with analgesic properties and the preparation and use thereof
US4435449A (en) Treatment of minimal brain dysfunction (MBD)
Covell et al. Chemotherapy of malaria
US6051587A (en) Treatment of iatrogenic and age-related hypertension and pharmaceutical compositions useful therein
US3773955A (en) Analgetic compositions
Abshagen et al. First data on effects and pharmacokinetics of isosorbide-5-mononitrate in normal man
US3795739A (en) Treatment of parkinson disease
US5750537A (en) Use of 5HT3 antagonist to treat impotence
US5006560A (en) Use of GABA-B selective agonists as anti-tussive agents
US6419959B1 (en) Galenic composition containing opioid antagonists
Longino et al. An orally effective quaternary amine, Banthine, capable of reducing gastric motility and secretions
Borody et al. Effects of morphine and atropine on motility and transit in the human ileum
US4438138A (en) Reduction of cholesterol with meta-chloro α-t-butylaminopropiophenone
US5057519A (en) 5-HT3 antagonists: use in reducing opiate tolerance
Franz Clinical trials with thiabendazole against human strongyloidiasis