From the Guidelines
Diphenoxylate acts as an agonist at mu (μ) opioid receptors, producing strong analgesia and other effects such as constipation, respiratory depression, and euphoria 1.
Mechanism of Action
- Diphenoxylate's action on mu opioid receptors results in analgesia mediated through brain mechanisms and spinal mechanisms 1.
- The effects of diphenoxylate on mu opioid receptors also include respiratory depression, which can be dose-dependent and lead to decreased responsiveness of ventilatory centers to carbon dioxide 1.
- Other effects of diphenoxylate's action on mu opioid receptors include constipation, due to delayed gastric emptying and peristalsis, and euphoria, which can contribute to its potential for abuse and addiction 1.
Clinical Considerations
- The use of diphenoxylate and other opioids requires careful consideration of the potential risks and benefits, including the risk of tolerance, physical dependence, and addiction 1.
- Diphenoxylate's narrow therapeutic index and wide interpatient range of necessary dose require careful dosing and monitoring to minimize adverse effects 1.
- As with other opioids, diphenoxylate should be used with caution in patients with a history of substance abuse or addiction, and alternative treatments should be considered when possible 1.
From the FDA Drug Label
Diphenoxylate hydrochloride is chemically related to the narcotic analgesic meperidine. Diphenoxylate hydrochloride is devoid of morphine-like subjective effects at therapeutic doses. At high doses it exhibits codeine-like subjective effects.
The effect of Diphenoxylate on mu (μ) opioid receptors is not directly stated in the label. However, the fact that it is chemically related to meperidine, a known opioid, and exhibits codeine-like subjective effects at high doses, suggests that it may have some activity at these receptors.
- Key point: The label does not provide direct information on the effect of diphenoxylate on mu opioid receptors.
- Clinical decision: Given the lack of direct information, it is unclear what effect diphenoxylate has on mu opioid receptors, but its chemical relation to meperidine and codeine-like effects at high doses suggest possible interaction 2.
From the Research
Effect of Diphenoxylate on Mu (μ) Opioid Receptors
- Diphenoxylate is a mu receptor agonist that has been shown to slow gastrointestinal transit by its effects on the circular and longitudinal muscle of the intestine 3.
- As a mu receptor agonist, diphenoxylate has an effect on the mu opioid receptors, which are involved in the regulation of various physiological processes, including pain modulation and gut function 3, 4, 5, 6.
- The activation of mu opioid receptors by diphenoxylate can produce analgesic effects, as well as other behavioral effects such as constipation and respiratory depression 3, 7, 5.
- Diphenoxylate, unlike other mu receptor agonists such as morphine, does not have a significant effect on the central nervous system, making it useful for the treatment of diarrhea in irritable bowel syndrome (IBS) patients 3.
Comparison with Other Mu Opioid Receptor Agonists
- Diphenoxylate has a similar mechanism of action to other mu opioid receptor agonists, such as morphine and loperamide, but with a different pharmacological profile 3, 4, 5.
- The development of novel opioid analgesics, including biased agonists and allosteric modulators, may provide new strategies for the treatment of pain and other conditions, with potentially fewer side effects than traditional mu opioid receptor agonists like diphenoxylate 4, 5.