Dopamine-2 receptors 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... 

These symptoms are alleviated by administering levodopa (L-dopa), a precursor for dopamine. L-dopa is taken up by the axon terminals of dopaminergic neurons and used to form dopamine. Interestingly, in some patients, a side effect of dopamine replacement therapy is the development of symptoms characteristic of schizophrenia. (Recall that this mental disorder is caused by overactive dopaminergic neurons.) On the other hand, drugs used to treat schizophrenia — dopamine receptor antagonists — may elicit symptoms of Parkinson s disease. 

Ponzoni, A., Monti, J. M., Jantos, H., Altier, H. Monti, D. (1995). Increased waking after intra-accumbens injection of m-chlorophenylbiguanide prevention with serotonin or dopamine receptor antagonists. Eur. J. Pharmacol. 278, 111-15. 

Anderson S.M., Bari A.A., Pierce R.C. Administration of the Dl-like dopamine receptor antagonist SCH-23390 into the medial nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug-seeking behavior in rats. Psychopharmacology (Berlin). 168 132, 2003. 

Telia S. Differential blockade of chronic versus acute effects of intravenous cocaine by dopamine receptor antagonists. Pharmacol. Biochem. Behav. 48 151, 1994. 

Shimosato K., Marley R., Saito T. Differential effects of NMDA receptor and dopamine receptor antagonists on cocaine toxicities. Pharmacol. Biochem. Behav. 51, 1995. 

Altier, N., and Stewart, J., Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine, J. Pharmacol. Exp. Ther., 285, 208, 1998. 

Metoclopramide is a dopamine receptor antagonist, which acts selectively on the chemoreceptor trigger zone. 

Mechanism of Action A dopamine receptor antagonist that stimulates motility of the upper G1 tract and decreases reflux into the esophagus. Also raises the threshold of activity in the chemoreceptor trigger zone. Therapeutic Effect Accelerates intestinal transit and gastric emptying relieves nausea and vomiting. 

Is a central nervous system (CNS) dopamine-receptor antagonist Has cholinomimetic properties Has sedative properties... 

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