Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis (delayed gastric emptying). It raises the level of prolactin in the human body and is used to induce and promote breast milk production. It may be taken by mouth or rectally.
Side effects of domperidone include headache, dry mouth, abdominal cramps, diarrhea, and elevated prolactin levels. Secondary to increased prolactin levels, breast changes, milk outflow, menstrual irregularities, and hypogonadism can occur. Domperidone may also cause QT prolongation and has rarely been associated with serious cardiac complications such as sudden cardiac death. However, the risks are small and occur more with high doses. Domperidone acts as a peripherally selective antagonist of the dopamine D2 and D3 receptors. Due to its low entry into the brain, the side effects of domperidone are different from those of other dopamine receptor antagonists like metoclopramide and it produces little in the way of central nervous system adverse effects. However, domperidone can nonetheless increase prolactin levels as the pituitary gland is outside of the blood–brain barrier.
Domperidone was discovered in 1974 and was introduced for medical use in 1979. It was developed by Janssen Pharmaceutica. Domperidone is available over-the-counter in many countries, for instance in Europe and elsewhere throughout the world. It is not approved for use in the United States. However, it is available in the United States for people with severe and treatment-refractory gastrointestinal motility problems under an expanded access individual-patient investigational new drug application. An analogue of domperidone called deudomperidone is also currently under development for potential use in the United States and other countries.
There is some evidence that domperidone has antiemetic activity. It is recommended by the Canadian Headache Society for treatment of nausea associated with acute migraine.
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Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic.
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D6, a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body.
Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non-selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antagonist of 5-HT2 and α-adrenergic receptors with high affinity. The compound is historically a morphine decomposition product made by boiling morphine with concentrated acid, hence the -morphine suffix. Contrary to its name, apomorphine does not actually contain morphine or its skeleton, nor does it bind to opioid receptors.
Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated alpha-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of do ...
In order to understand the link between substantia nigra pars compacta (SNc) cell loss and Parkinson's disease (PD) symptoms, we developed a multiscale computational model that can replicate the symptoms at the behavioural level by incorporating the key ce ...
FRONTIERS MEDIA SA2022
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ObjectivesTo provide an automated classification method for degenerative parkinsonian syndromes (PS) based on semiquantitative I-123-FP-CIT SPECT striatal indices and support-vector-machine (SVM) analysis.Methods(123)I-FP-CIT SPECT was performed at a singl ...