Generalities and Therapeutic Indications
Prokinetic drugs are active ingredients used to selectively stimulate the motility of the stomach and intestines.
Furthermore, some of the most commonly used prokinetic drugs in therapy are also capable of exerting an antiemetic action.
Mechanism of action
There are different types of prokinetic drugs, which perform their activity with different mechanisms of action.
In any case, in principle it can be said that these active ingredients carry out their prokinetic action by interacting with specific receptors located along the gastrointestinal tract.
These receptors are:
- Dopaminergic receptors; by antagonizing these receptors, prokinetic drugs are able to increase the tone of the intestinal smooth muscle, thus promoting its motility.
- Cholinergic receptors (or muscarinic if you prefer); some prokinetic drugs are agonists of this type of receptors, therefore they are endowed with sympathomimetic activity. The activation of the muscarinic receptors in the gastrointestinal tract stimulates the contraction of the smooth muscles of the gastrointestinal tract, increasing its motility and favoring the expulsion of its contents.
- 5-HT4 serotonergic receptors; some prokinetic drugs act at the level of these receptors, exerting an agonist action against them. In this way, they stimulate peristalsis and gastrointestinal emptying.
Furthermore, many prokinetic drugs are also endowed with antiemetic activity, exerted through the antagonization of D2 receptors centrally in the Chemoreceptor Trigger Zone (or CTZ, an area of the medulla oblongata involved in the modulation of the activity of the vomiting center) and through the antagonization of the 5-HT3 serotoninergic receptors, present both centrally in the CTZ, and in the gastrointestinal tract.
Types of Prokinetic Drugs
As mentioned, there are different types of prokinetic drugs that can be used to promote and increase gastrointestinal peristalsis.
These drugs will be briefly explained below.
Bethanechol
Bethanechol (no longer available in Italy) is an active principle with a direct parasympathomimetic action. This means that this molecule is able to directly stimulate the cholinergic receptors present at the gastrointestinal level.
Besides being used in the treatment of gastrointestinal hypotonia, betanechol is also indicated for the treatment of bladder hypotonia.
Metoclopramide
Metoclopramide (Plasil®, Geffer®), on the other hand, belongs to the category of prokinetic drugs also endowed with antiemetic activity. In fact, this molecule is an "agonist of 5-HT4 serotonin receptors present in the gastrointestinal tract and, at the same time, antagonizes the D2 and 5-HT3 receptors present in the CTZ and in the gastrointestinal tract.
Metoclopramide exerts its prokinetic activity mainly at the gastric level. However, its main therapeutic indications remain the treatment and prophylaxis of nausea and vomiting (including those induced by chemotherapy and antineoplastic radiotherapy, headache and surgery).
Levosulpiride
Levosulpiride (Levopraid®) possesses a mechanism of action very similar to that of metoclopramide, ie it exerts an "agonist action against 5-HT4 receptors and an" antagonist action against dopaminergic D2 receptors. Therefore, this active principle is capable of also exercising an "antiemetic activity.
Similarly to what happens with the use of metoclopramide, sulpiride exerts its prokinetic action especially at the gastric level. In fact, one of its main therapeutic indications consists in the treatment of dyspeptic syndrome due to delayed gastric emptying.
Domperidone
Domperidone (Peridon®, Domperidone ABC®, Motilium®) is another of those prokinetic drugs also endowed with antiemetic activity.
In this case, however, the prokinetic action is exerted through the antagonization of the dopaminergic receptors present at the gastrointestinal level. This antagonization, in fact, allows to accelerate gastric emptying and to increase intestinal tone and peristalsis.
Dexpanthenol
Dexpanthenol (Bepanten®) is a drug used in the treatment of intestinal atony. This active principle carries out its activity through a singular mechanism of action.
In fact, dexpanthenol is nothing more than the dextrorotatory enantiomer of alcohol obtained from pantothenic acid (also known as vitamin B5). Pantothenic acid is essential for the synthesis of acetyl-coenzyme A (or acetyl-CoA) which , in turn, it is indispensable for the synthesis of acetylcholine.
Once taken, dexpanthenol is converted to pantothenic acid which will then be used to synthesize acetyl-coenzyme A and, consequently, acetylcholine.
Therefore, dexpanthenol - although not properly included in the class of prokinetic drugs - is able to promote intestinal peristalsis through indirect stimulation of cholinergic transmission.
Side effects
Of course, the type of side effects and the intensity with which they occur may vary according to the type of active ingredient used and according to the sensitivity of each patient towards the drug used.
Broadly speaking, however, it can be stated that the main undesirable effects caused by prokinetic drugs are caused by the action of these same active ingredients also at the central level (thanks to their ability to cross the blood brain barrier) and not only at the peripheral level (in this case, at the gastrointestinal level).
For example, prokinetic drugs such as metoclopramide can cause adverse effects such as restlessness, movement disorders and fatigue. While neostigmine can cause drowsiness, headache, dizziness, seizures and loss of consciousness.
Domperidone, on the other hand, is unable to cross the blood brain barrier, therefore, it causes fewer unwanted effects.
Of course - as with any other active ingredient - the use of prokinetic drugs can also cause hypersensitivity reactions in sensitive subjects.
