Dopamine antagonists domperidone

Another cardiac response to catecholamine release is Increased vulnerability to ventricular fibrillation. Recent studies (13) have shown that bromocriptine produced an increase of 50% in the ventricular fibrillation threshold In anesthetized dogs, and that pretreatment with the peripheral D-2 dopamine antagonist domperidone abolished this effect. This suggests that adrenergic induced cardiac arrhythmia may be inhibited by peripheral presynaptic dopamine agonists. 

Brendemuhl J, Cross D 1998 Influence of the dopamine antagonist domperidone on the vernal transition in seasonally anestrus mares. In Proceedings of the 7th International Symposium on Equine Reproduction, Pretoria, pp. 47-48... 

Motilium contains domperidone, v/hich is a dopamine antagonist and acts on the chemoreceptor trigger zone. It is ineffective in motion sickness. Stugeron contains cinnarizine Avomine and Phenergan contain promethazine and Kwells contains hyoscine hydrobromide. Cinnarizine and promethazine are antihistamines, which are indicated in motion sickness and hyoscine hydrobromide is an antimuscarinic agent that is also used in motion sickness. 

Q53 Domperidone may be used to prevent motion sickness. Domperidone is a dopamine antagonist that acts at the chemoreceptor trigger zone. 

Domperidone is a dopamine antagonist that acts on the chemoreceptor trigger zone. It can therefore be used as an anti-emetic in nausea and vomiting, for example, to counteract side-effects of cytotoxic therapy and to treat nausea associated with dopaminergic drugs used in Parkinson s disease. Unlike hyoscine butlybromide and antihistamines, domperidone is ineffective in motion sickness. 

Prophylactic administration of antiemetics is essential in any patient receiving FOLFOX chemotherapy. The combination of oxaliplatin and 5-fluorouracil results in a moderate level of emetogenicity and requires the administration of 5HT3-receptor antagonists and corticosteroid treatment, generally with a dopamine antagonist such as metoclopramide or domperidone. Severe manifestations may have to be managed by delay and/or dose modification of the patient s next cycle of chemotherapy. 

The p.o. administration of the dopamine antagonists such as domperidone (see p. 184) promotes... 

Strickland et al. (1991, 1994) studied the effects of ergot and loline alkaloids of E+ fescue on prolactin release by isolated and perfused rat pituitary cells. The ergot alkaloids had prolactin-lowering effects and mimicked dopamine action. The use of a D2 dopamine receptor antagonist (domperidone) blocked the effect of the ergot alkaloids and prevented their prolactin-lowering effect. Domperidone... 

NB Oliviera CR, Lima MCP, Carvalho CAM, Leysen JE and Carvalho AP, Partition coefficients of dopamine antagonists in brain membranes and liposomes, Biochem. Pharmacol., 38, 2113-2120 (1989) gave a value of 8.66 refered to Leysen JE, Gommeren W, J. Neurochem., 36, 201-219 (1981) also Pauwels PJ, Leysen JE and Laduron PM, Eur. J. Pharmacol., 124, 291-298 (1986). Also referred to spiperone, pimozide, and domperidone. 

Note that prochlorperazine should not be given if apomorphine is used for Parkinson s disease, as its dopamine antagonist actions can worsen the disease (see also Levodopa + Antiemetics , p.682). Because apomorphine is highly emetogenic at the doses required for the treatment of Parkinson s disease (1 to 4 mg/hour by subcutaneous infusion), patients with Parkinson s disease requiring apomorphine should be pretreated with domperidone 20 mg three times daily for at least 2 days. Rare reports of extrapyramidal adverse effects have been reported with ondansetron, which may be of relevance in patients with Parkinson s Disease. 

Domperidone is a dopamine antagonist similar to metoclopramide. However, since it acts on the dopamine receptors in the stomach wall, and unlike metoclopramide, it does not readily cross the blood-brain barrier, it does not appear to oppose the effects of levodopa within the brain, although some extrapyramidal symptoms have been observed. It may even slightly increase the bioavailability and effects of levodopa (by stimulating gastric emptying). Domperidone can therefore be used to control the nausea and vomiting associated with levodopa treatment of Parkinson s disease. 

Domperidone [133], one of the most potent D2-dopamine blockers and antagonists of apomorphine-induced emesis with limited brain-blood barrier permeability, did not establish a position as an antiemetic, especially against cisplatin [134], Recently, the use of domperidone as a parenteral antiemetic has been discontinued because of serious cardiovascular toxicity. 

Metoclopramide may be considered as a prototype 5-HT3 antagonist because its antiemetic efficacy both in animals and man could not be adequately explained by D2-dopamine blockade. In fact, metoclopramide was considerably weaker as a D2-antagonist than haloperidol or domperidone and yet it was effective against emesis induced by anticancer agents both in animals [43, 80] and cancer patients [135]. 

Die specificity of the dopamine receptor was further studied with a series of dopaminergic antagonists of well known pharmacological activity. The 30-40% inhibitory effect of 10 nM dopamine was completely reversed by the addition of increasing concentrations of the potent neuroleptics (+)butaclamol (Kp = 1.5 nM) and (-)sulpiride (Kp = 0.5 nM) while their pharmacologically weak enantiomers (-)butaclamol and (+)sulpiride were 86 and 167 times less potent, respectively. The neuroleptics spiroperidol, thioproperazine, domperidone, haloperidol, fluphenazine and pimozide completely reversed the inhibitory effect of dopamine at low Kp values ranging from 0.02 to 0.8 nM (41). 

Antiemetics. Stimulation of dopamine receptors in the area postrema can elicit vomiting. D2 receptor antagonists such as meto-clopramide and domperidone are used as antiemetics (p.342). In addition they promote gastric emptying. 

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