Novel Therapeutic Options Uncovered By Khat Chewing

Main Category: Respiratory / Asthma
Article Date: 29 Aug 2008 - 0:00 PDT

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Fresh khat (Catha edulis) leaves have been chewed for centuries in eastern Africa and in the Arabian Peninsula in order to reach a state of euphoria and stimulation. This is due to its main active constituent, cathinone, which increases the release of catecholamines in the brain, evoking an "ampthetamine-like" effect. In these countries, khat has been traditionally used as a social drug.

However, new patterns of khat consumption are now emerging in these countries, and the development of air transportation has contributed to the spread of this habit to the rest of the world. Khat growing, distribution and use are therefore becoming an international issue, as shown by the significant press interest in this substance. Interestingly, fresh khat leaves prepared as an infusion in some African countries are considered a traditional remedy for airway diseases, but until now the precise mechanism of action underlying this effect was unknown.

In this study, Maria Belvisi (National Heart and Lung Institute, Imperial College School of Medicine, London, UK) and her colleagues highlight an inhibitory action of this natural product on cholinergic contractile responses of guinea pig and human airway smooth muscle, and reveal its mechanism of action, thereby uncovering new therapeutic options for the treatment of airway diseases.

This study is the first to address how khat, when used as a traditional remedy, can alleviate respiratory disease symptoms. It shows that cathinone targets both post-ganglionic, pre-junctional a2 adrenergic and 5-HT7 receptors to inhibit the release of acetylcholine from parasympathetic nerves innervating the airways, thereby modulating the neural control of airway constrictor tone.

In revealing this dual mechanism of action for cathinone, this study may provide key information for the development of new treatment options for airway diseases displaying heightened cholinergic tone, such as asthma associated with gastro-oesophageal reflux, nocturnal asthma or chronic obstructive pulmonary disease (COPD).

Indeed, in COPD in particular, increased parasympathetic drive is responsible for increased bronchial smooth muscle tone and excessive mucus production. Muscarinic antagonists (also known as anti- cholinergics, e.g. ipratropium and tiotropium) are particularly effective as bronchodilators in the treatment of COPD where the vagal tone appears to be the only reversible component of airflow limitation. In this respect, the development of new anti-cholinergic molecules based on a mechanism of action other than antagonising muscarinic receptors may be of particular interest in the treatment of airway diseases with heightened cholinergic tone.

Therefore, cathinone, with its original dual pre-junctional mechanism of action, may lead to the development of novel therapeutic approaches for the treatment of such diseases.

Title Of The Original Article
Modulation of cholinergic contractions of airway smooth muscle by cathinone: potential beneficial effects in airway diseases

The European Respiratory Journal is the peer-reviewed scientific publication of the European Respiratory Society (more than 8,000 specialists in lung diseases and respiratory medicine in Europe, the United States and Australia).

European Respiratory Journal

The European Respiratory Society (ERS)