Plant extracts and alkaloids having antitussive activity

Abstract

The present invention provides plant extracts, isolated alkaloids, synthetic alkaloids and compositions having antitussive activity. In some preferred embodiments, the plant extracts and the isolated alkaloids are from a plant of a genus in the family Stemonaceae. In other preferred embodiments, the plant extracts and the isolated alkaloids are from a plant of the genus Stemona, Croomia, or Stichoneuron. In especially preferred embodiments, the plant extracts and the isolated alkaloids are from the plant Stemona tuberosa. The present invention further provides methods for isolating such plant extracts and alkaloids. In addition, the present invention provides methods for reducing or suppressing coughing by administering plant extracts, alkaloids and compositions having antitussive activity.

Description

FIELD OF THE INVENTION [0001] This invention pertains to the field of plant extracts, isolated plant alkaloids, and synthetic alkaloids that have antitussive activity and which are useful as pharmaceutical agents for reducing or suppressing coughing. BACKGROUND OF THE INVENTION [0002] Coughing provides a means for clearing the tracheal and bronchial trees of accumulated secretions and / or foreign bodies. The mechanism of coughing is initiated by an appropriate stimulus which elicits a deep inspiration, followed by closure of the epiglottis and relaxation of the diaphragm. Thereafter, a sharp muscle contraction against the closed epiglottis occurs, thereby, producing increased pressure in the intra-thoracic and intra-airway passages. The positive intra-thoracic pressure causes a narrowing of the trachea due to enfolding of its compliant posterior membrane and opens the epiglottis. When the epiglottis opens, the combination of the large pressure differential between the thoracic cavity...

AI Technical Summary

Benefits of technology

[0014] In another embodiment, the present invention provides a method for reducing coughing in a subject, the method comprising: administering a pharmaceutically effective amount of a compound having Formula I: wherein: R1 is selected from a hydrogen and an α(S)-methyl-γ(S)-butyroylactonyl; R2 is selected from a β-oriented hydrogen and an α-oriented hydrogen; R3 is selected from a β-oriented hydrogen and an α-oriented hydrogen; R4 is hydroxyl; R5 is selected from a hydroxymethyl and a carboxyl. In an alternative embodiment, R4 and R5 together with the carbons to which they are attached, join to form a substituted γ(S)-butyroylactonyl or substituted furane ring; and R6 is selected from a β-oriented hydrogen and an α-oriented hydrogen. In another embodiment, R4 and R5 together with the carbons to which they are attached, join to form a substituted γ(S)-butyroylactonyl and R2 and R6 are both absent and form a pyrrole ring, provided however, that when R1 is α(S)-methyl-γ(R)-butyroylactonyl, R3 is an α-oriented hydrogen, thereby reducing coughing in a subject.

Problems solved by technology

Further, mechanical stimuli, for example the inhalation of particulate matter, can cause coughing.

Other mechanical disorders which result in compression of the air passages or increased pressure upon any area of the respiratory system may result in coughing.

Such mechanical difficulties may arise from intra-mural or extra-mural etiologies.

Decreased pliancy of the respiratory membranes may also result in chronic coughing, as in the case of patients suffering from cystic fibrosis.

Other chemical entities result in coughing due to their reactive effect upon the respiratory system itself or on the balance and uptake of respiratory gases.

Additionally, many chemical agents induce coughing due to their reaction with enzymes involved in the respiratory process.

Lastly, thermal stimuli, such as the inhalation of either very hot or cold air, may also result in coughing.

For example, patients suffering from bronchial asthma can result in incessant coughing.

Moreover, the violent contractions of the thoracic cavity which accompany coughing further aggravates already irritated respiratory membranes.

However, these compounds have adverse side effects.

For example, the use of morphine-like compounds are known to result in addiction, respiratory suppression, and inhibitory action of smooth muscle contraction (e.g., resulting in constipation), and psychotomimetics.

In particular, codeine is known to be highly addictive and dextromethorphan is known to induce hallucinations, delusions, or other symptoms of a psychosis.

Moreover, drugs having strong antitussive activity, for example codeine and dextromethorphan, are known to adversely act on the central nervous system.

Further, drugs that act on opioid receptors are known to adversely effect urination (Leander et al.

However, the number of safe and effective antitussive agents devoid of unwanted side effects, for example, sedation and addiction, is limited.

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