Mitemcinal (GM-611 or 3'-N-dimethyl-11-deoxy-3'-N-isopropyl-12-O-methyl-11-oxo-8,9-didehydroerythromycin) is a
motilin
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the ''MLN'' gene.
Motilin is secreted by endocrine Mo cells (also referred to as M cells, which are not the same as the M cells, or microfold c ...
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
derived from the
macrolide antibiotic,
erythromycin
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used du ...
. It was discovered in the labs of
Chugai Pharma. Mitemcinal is orally administered and it is believed to have strong promotility (or prokinetic) effects. Promotility drugs relieve symptoms of reflux by speeding the clearance of acid from the oesophagus and stomach. The parent compound, erythromycin, has these characteristics, but mitemcinal lacks the antibiotic properties of erythromycin.
Presently, erythromycin is commonly used off-label for gastric motility indications such as
gastroparesis
Gastroparesis (gastro- from Ancient Greek γαστήρ – gaster, "stomach"; and -paresis, πάρεσις – "partial paralysis"), also called delayed gastric emptying, is a medical disorder consisting of weak muscular contractions ( peristalsis) ...
. If mitemcinal can be shown to be as effective a promotility agent, it would represent a significant advance in the GI field as treatment with this drug would not carry the risk of unintentional selection of antibiotic-resistant bacteria. This concept greatly intrigued Chugai, and the company pursued it as an ideal candidate for a long-term prokinetic agent to treat lower
gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
deficiencies including gastroparesis.
The Phase II trials did not detect an increase in gastric emptying among the population of diabetic gastroparesis patients above placebo.
[ The Conclusion of the cited reference does not indicate that there was no benefit. On the contrary, the study said there was an increase in gastric emptying. ] Thus, although Chugai was able to demonstrate the required safety of the compound, development of this drug has stalled due to a lack of convincing efficacy data.
Notes and references
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Macrolides