Monoamine oxidase (MAO) inhibitors and uses thereof

Abstract

The present invention provides a group of tobacco alkaloids, tobacco extract, Yerbamaté extract, and an extract of chewing gum and lozenges which are modulators of monoamine oxidase (MAO) activity (i.e., compounds and substances which inhibit MAO enzyme and prevent its biological activity). The MAO inhibitors of the present invention can cause an increase in the level of norepinephrine, dopamine, and serotonin in the brain and other tissues, and thus can cause a wide variety of pharmacological effects mediated by their effects on these compounds. The MAO inhibitors of the present invention are useful for a variety of therapeutic applications, such as the treatment of depression, disorders of attention and focus, mood and emotional disorders, Parkinson's disease, extrapyramidal disorders, hypertension, substance abuse, smoking substitution, anti-depression therapy, eating disorders, withdrawal syndromes, and the cessation of smoking.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a division of application Ser. No. 10 / 396,319, filed Mar. 26, 2003, which is a division of application Ser. No. 10 / 042,164, filed Jan. 11, 2002, now U.S. Pat. No. 6,569,470, which is a division of application Ser. No. 09 / 325,852, filed Jun. 4, 1999, now U.S. Pat. No. 6,350,479, which claims priority under 35 U.S.C. § 119(e) to Provisional Application No. 60 / 088,117, filed Jun. 5, 1998.FIELD OF THE INVENTION

[0002] The present invention relates to the novel use of compounds and substances which are capable of modulating monoamine oxidase (MAO) activity by inhibiting the MAO enzyme. The present invention also relates to MAO inhibitors and their therapeutic use as a drug or dietary supplement in the treatment of various conditions or disorders, including psychiatric and neurological illnesses. More particularly, the present invention relates to the therapeutic use of tobacco alkaloids, Yerbamaté (Ilex paraguariensis) ex...

Examples

example 1

[0058] Anabasine, in its purified form, was dissolved in distilled water in a maximal inhibition concentration of 0.2 mg / ml, and tested according to the procedure described above. At maximal or saturating inhibition concentrations, anabasine was effective at inhibiting MAO activity by approximately 10-13%, and was effective at inhibiting the enzyme at all time points in the reaction.

[0059]FIG. 1 presents the means (plus or minus the standard errors of the means) for the percent inhibition of MAO activity produced by saturating concentrations of anabasine over 60 minutes of MAO activity measured as described above. Each data point represented the mean of 5 determinations. All the data points shown in FIG. 1 were statistically, significantly different from the sham control at each time point tested (student t test, p<0.01), and were representative of multiple experiments.

[0060] Since anabasine was an inhibitor of MAO activity, further studies were conducted to evaluate if this agent...

example 2

[0061] Anatabine in its purified form, was dissolved in distilled water in a maximal inhibition concentration of 0.1 mg / ml, and tested according to the procedure described above. At maximal or saturating inhibition concentrations, anatabine was effective at inhibiting MAO activity by approximately 60%. This result shows that anatabine may be much safer as a medication than standard MAO enzyme inhibitors. Anatabine was effective at inhibiting the enzyme at all time points in the reaction, and was equally effective in inhibiting both MAO A and MAO B activities.

[0062]FIG. 3 presents the means (plus or minus the standard errors of the means) for the percent inhibition of MAO activity produced by saturating concentrations of anatabine over 60 minutes of MAO activity measured as described above. Each data point represented the mean of 6 determinations. Anatabine was an effective MAO inhibitor at maximal concentrations, inhibiting the enzyme by approximately 60%, as discussed above. All t...

example 3

[0064] Nornicotine in its purified form, was dissolved in distilled water in a maximal inhibition concentration of 0.08 mg / ml, and tested according to the procedure described above. At maximal or saturating inhibition concentrations, nornicotine was effective at inhibiting MAO activity by approximately 80 to 95%, and was effective at inhibiting the enzyme at all time points in the reaction. Nornicotine was also equally effective in inhibiting both MAO A and MAO B activities.

[0065]FIG. 5 presents the means (plus or minus the standard errors of the means) for the percent inhibition of MAO activity produced by saturating concentrations of nornicotine over 60 minutes of MAO activity measured as described above. Each data point represented the mean of 6 determinations. Nomicotine was an effective MAO inhibitor at maximal concentrations, inhibiting the enzyme by approximately 80-95%, as discussed above. All the data points shown in FIG. 5 were statistically, significantly different from ...

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a division of application Ser. No. 10 / 396,319, filed Mar. 26, 2003, which is a division of application Ser. No. 10 / 042,164, filed Jan. 11, 2002, now U.S. Pat. No. 6,569,470, which is a division of application Ser. No. 09 / 325,852, filed Jun. 4, 1999, now U.S. Pat. No. 6,350,479, which claims priority under 35 U.S.C. § 119(e) to Provisional Application No. 60 / 088,117, filed Jun. 5, 1998.FIELD OF THE INVENTION

[0002] The present invention relates to the novel use of compounds and substances which are capable of modulating monoamine oxidase (MAO) activity by inhibiting the MAO enzyme. The present invention also relates to MAO inhibitors and their therapeutic use as a drug or dietary supplement in the treatment of various conditions or disorders, including psychiatric and neurological illnesses. More particularly, the present invention relates to the therapeutic use of tobacco alkaloids, Yerbamaté (Ilex paraguariensis) ex...

Examples

example 1

[0058] Anabasine, in its purified form, was dissolved in distilled water in a maximal inhibition concentration of 0.2 mg / ml, and tested according to the procedure described above. At maximal or saturating inhibition concentrations, anabasine was effective at inhibiting MAO activity by approximately 10-13%, and was effective at inhibiting the enzyme at all time points in the reaction.

[0059]FIG. 1 presents the means (plus or minus the standard errors of the means) for the percent inhibition of MAO activity produced by saturating concentrations of anabasine over 60 minutes of MAO activity measured as described above. Each data point represented the mean of 5 determinations. All the data points shown in FIG. 1 were statistically, significantly different from the sham control at each time point tested (student t test, p<0.01), and were representative of multiple experiments.

[0060] Since anabasine was an inhibitor of MAO activity, further studies were conducted to evaluate if this agent...

example 2

[0061] Anatabine in its purified form, was dissolved in distilled water in a maximal inhibition concentration of 0.1 mg / ml, and tested according to the procedure described above. At maximal or saturating inhibition concentrations, anatabine was effective at inhibiting MAO activity by approximately 60%. This result shows that anatabine may be much safer as a medication than standard MAO enzyme inhibitors. Anatabine was effective at inhibiting the enzyme at all time points in the reaction, and was equally effective in inhibiting both MAO A and MAO B activities.

[0062]FIG. 3 presents the means (plus or minus the standard errors of the means) for the percent inhibition of MAO activity produced by saturating concentrations of anatabine over 60 minutes of MAO activity measured as described above. Each data point represented the mean of 6 determinations. Anatabine was an effective MAO inhibitor at maximal concentrations, inhibiting the enzyme by approximately 60%, as discussed above. All t...

example 3

[0064] Nornicotine in its purified form, was dissolved in distilled water in a maximal inhibition concentration of 0.08 mg / ml, and tested according to the procedure described above. At maximal or saturating inhibition concentrations, nornicotine was effective at inhibiting MAO activity by approximately 80 to 95%, and was effective at inhibiting the enzyme at all time points in the reaction. Nornicotine was also equally effective in inhibiting both MAO A and MAO B activities.

[0065]FIG. 5 presents the means (plus or minus the standard errors of the means) for the percent inhibition of MAO activity produced by saturating concentrations of nornicotine over 60 minutes of MAO activity measured as described above. Each data point represented the mean of 6 determinations. Nomicotine was an effective MAO inhibitor at maximal concentrations, inhibiting the enzyme by approximately 80-95%, as discussed above. All the data points shown in FIG. 5 were statistically, significantly different from ...

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