New angle for potential asthma therapies

RESEARCH & DEVELOPMENT

The increasing understanding of the effects of neuropeptides in the lung may bring us closer to new approaches for the treatment of asthma.

A large number of neuropeptides with potent effects on the lung have been reported. The most promising is vasoactive intestinal peptide (VIP), which is the most potent endogenous bronchodilator known.

VIP is also a potent pulmonary vasodilator and stimulates mucous secretion. It has the ability to relax tracheobronchial smooth muscle and to inhibit bronchoconstriction induced by inflammatory mediators. However, inhaled VIP has had minimal affect in patients with asthma; this is thought to be caused by rapid degradation. Combining VIP with enzyme inhibitors, or the use of more stable analogues may overcome this.

Other neuropeptides include the tachykinin, substance P, which causes contraction of airway smooth muscle, stimulates mucous secretion and may also promote mast cell degranulation. Calcitonin gene-related peptide, frequently colocalised with substance P, causes bronchial smooth muscle contraction and also affects blood flow regulation. Endothelin-l (ET-l) is an extremely potent bronchoconstrictor and pulmonary vasoconstrictor, and may be released in the airways of asthmatics.

Modulation of the sensory neuropeptides may also have therapeutic potential. For example, if neurogenic inflammation proves to be important in asthma, then inhibitors of tachykinin may be very useful. Boomsma JD. Said S1. The role of neuropeptides in asthma. Chest 101 (Suppl. ): 389-392, Jun 1992 ""''''''''''

ISSN 0156-2703/92/0718-0011/$1.00'" Adis International Ltd

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INPHARMA' 18 Jul1992