Antiemetics dopamine-receptor antagonists

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

A subcategory of dopamine receptor antagonists has found some use as antiemetic agents administered in conjunction with antimmor chemotherapy. The preparation of one of these agents based on a benzotriazole nucleus begins with nitration of the amino salicylate ester (67-1). Catalytic hydrogenation of the product (67-2) leads to the orf/zo-diamine (67-3). Treatment of this last product with nitrous acid... 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

NERVOUS SYSTEM DRUGS ANTIEMETICS Dopamine receptor antagonists... 

Cisapride is structurally similar to metoclopramide, but has no dopamine receptor antagonist activity and hence no central antiemetic effect. However, because it stimulates the release of acetylcholine in the gastrointestinal tract it is effective in conditions such as reflux esophagitis and gastroparesis. During clinical trials, the most frequent unwanted effects were diarrhea (5-11%) and abdominal pain (16% with 20 mg bd). 

Domperidone is a neuroleptic antiemetic, a dopamine receptor antagonist. It produces the expected range of dystonic and extrapyramidal adverse effects (1), which seem, as with metoclopramide, to be more likely to occur in children (2). It is difficult to accept that claims for lower frequencies than with metoclopramide are justified, particularly when one reads a report of neuroleptic malignant sjmdrome (3). Like its congeners, domperidone has repeatedly been shown to cause sjmptoms attributable to hyperprolactinemia (galactorrhea, amenorrhea, and breast tenderness), despite claims that there is a lower incidence of effects on prolactin concentrations. However, a study in patients with Parkinson s disease using domperidone did not suggest that the adverse effects are especially problematical in these patients (4). 

Clebopride [inn. usan] (cleboprlde n-ialate [jan]) is a substituted benzamide, a (Dj) DOPAMINE RECEPTOR ANTAGONIST, and has activity as a visceral ANTISPASMODIC and antinauseant and antiemetic. 

Vomiting is triggered in the chemoreceptor trigger zone of the medulla, and nearly all dopamine receptor agonists (e.g. bromocriptine), and agents that increase dopamine in the brain (e.g. levodopa), cause vomiting. Conversely, many dopamine receptor antagonists (e.g. metoclopramide, and phenothiazines, e.g. chlorpromazine and prochlorperazine) have antiemetic activity. 

SUltopride [inn] (sultopride hydrochloride [jan] LIN 1418) is one of the substituted benzamides, with properties similar to sulpiride, and is a dopamine receptor antagonist. It has ANTIEMETIC actions, and has been used as an antipsychotic in the management of acute psychosis, sultopride hydrochloride sultopride. 

Trade names Evoxin Motilium (Johnson Johnson) Indications Investigational antiemetic, gastroesophageal reflux disease (GERD), nausea and vomiting Category Dopamine receptor antagonist Half-life 7-8 hours... 

Ondansetron is not a dopamine-receptor antagonist. Becanse serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone, it is not certain if ondansetron s antiemetic action is mediated centrally, peripherally, or in both sites (see Fignre 73). 

Nervous system There have been two reports of movement disorders induced by mirtazapine. Most of a case series of 14 patients with restless legs syndrome presented within a few days of starting treatment, and the symptom occurred more often in those who also took tramadol or dopamine receptor antagonists, such as antiemetics [72 ]. In one case, severe akathisia developed within 4 hours of a first... 

Neurokinin 1 (NKiJ-receptor antagonists have antiemetic properties that are mediated through central blockade in the area postrema. Aprepitant (an oral formulation) is a highly selective Nl -receptor antagonist that crosses the blood-brain barrier and occupies brain NKj receptors. It has no affinity for serotonin, dopamine, or corticosteroid receptors. Fosaprepitant is an intravenous formulation that is converted within 30 minutes after infusion to aprepitant. 

Substituted benzamides include metodopramide (discussed previously) and trimethobenzamide. Their primary mechanism of antiemetic action is believed to be dopamine-receptor blockade. Trimethobenzamide also has weak antihistaminic activity. For prevention and treatment of nausea and vomiting, metodopramide may be given in the relatively high dosage of 10-20 mg orally or intravenously every 6 hours. The usual dose of trimethobenzamide is 250 mg orally, 200 mg rectally, or 200 mg by intramuscular injection. The principal adverse effects of these central dopamine antagonists are extrapyramidal restlessness, dystonias, and parkinsonian symptoms. 

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