GUPTA COLLEGE OF TECHLOGICAL SCIENCES

Name: Ayan Gupta

Roll no. : 14
Dept.: Pharmacology
M.Pharm: 1st year, 1 semester
Assignment topic: New motilin receptor antagonist
drugs
Submitted to: Mr.Santanu Banerjee (Assistant professor GCTS)
Introduction
Motilin receptor agonists include the antibiotic erythromycin and other
agents—none of which is commonly available—that act as motilin
receptor ligands on smooth muscle cells and enteric nerves. The
pharmacodynamic effects in humans are dose-dependent. At low doses
(0.5 to 1 mg/kg as an intravenous bolus), erythromycin induces
sweeping gastric and intestinal peristaltic motor activity that resembles
phase III of the inter digestive migrating motor complex but may empty
the stomach inefficiently. At higher doses of 200 mg intravenously
used in clinical practice, antral activity becomes intense and empties
the stomach rapidly, although the burst of motility does not always
migrate down the small intestine. A simultaneous increase in small
bowel contractions may induce abdominal cramps and diarrhea.
Curiously, when used clinically as an antibiotic, erythromycin may
cause nausea and vomiting.
In clinical practice, erythromycin may be used to treat acute nausea and
vomiting associated with gastroparesis (diabetic, postsurgical, or
idiopathic) and to clear the stomach of retained food, secretions, and
blood prior to endoscopy. Erythromycin may be administered
intravenously in boluses of 200 to 400 mg every four to five hours. The
lower doses are more appropriate for patients with pseudo-obstruction,
which is associated with reduced inter digestive sweeping motor
activity in the small bowel.
Erythromycin is not suitable for prolonged treatment, because its
efficacy by the oral route is uncertain and its inherent antibiotic
properties carry the potential risk of complications, including
pseudomembranous colitis. New synthetic motilin agonists devoid of
antibiotic activity are in development.
Ghrelin is a peptide structurally and functionally related to motilin that
acts to accelerate postprandial gastric emptying. Ghrelin receptor
agonists may have a future therapeutic role as prokinetic agents for the
treatment of gastroparesis.
Motilin Receptor Antagonists
Targeted Approach
Motilin receptor antagonists, as the name suggests, work by inhibiting
the motilin receptor. By blocking this receptor, these drugs can
modulate gastrointestinal motility and provide targeted treatment for
specific disorders.
Broad Potential
The development of motilin receptor antagonists opens up new avenues
for therapeutic interventions in various gastrointestinal conditions,
including gastroparesis, functional dyspepsia, and irritable bowel
syndrome. These drugs hold the potential to alleviate symptoms and
improve patients' quality of life.
Mechanism of Action
Receptor Blockade
Motilin receptor antagonists bind to the motilin receptor, preventing
the activation of downstream signaling pathways. By blocking the
binding of motilin, these drugs inhibit the stimulation of
gastrointestinal smooth muscles and reduce excessive contractions.
Modulation of Gastric Emptying
Motilin receptor antagonists regulate gastric emptying by slowing
down or accelerating the movement of food from the stomach to the
small intestine. This modulation can be beneficial in conditions
characterized by delayed or rapid gastric emptying.
Clinical Applications
1. Gastroparesis
Motilin receptor antagonists offer a potential treatment
option for gastroparesis, a condition characterized by
delayed gastric emptying. By modulating motility, these
drugs can help improve symptoms such as bloating, early
satiety, and nausea.
2. Functional Dyspepsia:In functional dyspepsia, motilin
receptor antagonists may alleviate symptoms associated
with impaired stomach function, including postprandial
discomfort and pain. These drugs present an alternative
therapeutic approach for patients with this challenging
condition.
3. Irritable Bowel Syndrome
With their ability to modulate gastrointestinal motility, motilin
receptor antagonists hold potential for managing symptoms of
irritable bowel syndrome (IBS). By targeting the motilin receptor,
these drugs can help regulate bowel movements and provide relief
to individuals with IBS.
Conclusion/Future Direction
The development of new motilin receptor antagonist drugs
represents a significant advancement in the field of
gastroenterology. With their targeted approach, these medications
have the potential to revolutionize the treatment of
gastrointestinal motility disorders. Ongoing research and clinical
trials will further elucidate the efficacy, safety, and potential
expanded applications of motilin receptor antagonists, paving the
way for improved patient outcomes in the future