Non-ulcer dyspepsia - Z-338
Functional dyspepsia is one of the most common upper abdominal conditions. Sufferers experience chronic symptoms despite there being no obvious cause. It is believed to be a result of impaired gastric accommodation, delayed gastric emptying and visceral hypersensitivity. Current treatments are focused on speeding up the gastric emptying process with drugs such as domperidone, mosapride, cisapride and itopride. Their side-effects include extrapyramidal syndrome, severe adverse cardiovascular events and an increase in plasma prolactin levels.
A new gastroprokinetic agent with a lower side-effect profile has been discovered by the Japanese company Zeria Pharmaceuticals.1 Z-338 has been shown to have gastroprokinetic activity as good as cisapride, and it is more potent than mosapride, without severe adverse effects. While its mode of action is unclear, it seems to increase contraction and the release of acetylcholine, and inhibit acetylcholinesterase. It acts at muscarinic M1 and M2 receptors.
A Phase II multicentre randomised double-blind placebo-controlled parallel group pilot study has been carried out to examine its efficacy, safety and tolerability.2 A total of 62 patients who been experiencing the symptoms of functional dyspepsia for more than three months were given 50, 100 or 300mg of oral Z-338 three times a day for three weeks. It was found to be both safe and well tolerated, with the most common adverse event being headache. The 300mg dose of Z-338 gave a significant improvement over placebo in both mean and maximum post-meal gastric relaxation, and relaxation was also much better in four patients who suffered from impaired meal accommodation. However, it had no significant effect on either gastric sensitivity or gastric emptying at any of the doses investigated.
By the second week, patients given the 100mg dose saw significant improvements in bloating and global symptom scores. And heartburn and post-prandial fullness were much relieved in the same group by week three.
This group had significant improvements in the quality of life over those given placebo for both physical and social functioning. Further trials are to be carried out on Z-338, and if successful it could provide a solution from sufferers of this distressing condition.