Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets.

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Osinski MA, Uchic ME, Seifert T, Shaughnessy TK, Miller LN, Nakane M, Cox BF, Brioni JD, Moreland RB

Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets.

Pharmacol Biochem Behav. 2005 May;81(1):211-9.

PubMed ID

15894081 [ View in PubMed

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Abstract

Agents that activate the dopamine D2-like family of receptors elicit emesis in humans and other species with a vomiting/emetic reflex; however, the lack of dopamine receptor subtype selective agonists has hampered an understanding of which dopamine D2-like receptor subtype(s) contributes to the emetic response. In this study, stable cell lines expressing the ferret dopamine D2-long (D2L) and D4 receptors were used to characterize known dopamine agonists via radioligand binding and calcium ion flux assays, while emetic activity of these dopamine receptor agonists was determined in male ferrets. Latencies to first emetic event, average number of emetic episodes, and stereotypical behaviors which may be indicative of nausea were also determined. Agonists at dopamine D1-like and D4 receptors had no emetic effect in ferrets. Conversely, stimulation of dopamine D2 and/or D3 receptors resulted in a robust emetic response characterized by a relatively short latency (<15 min) and multiple emetic events. Competitive antagonists of dopamine D2-like receptors (domperidone, haloperidol) dose-dependently blocked the emetic response to PNU95666E, a dopamine D2 receptor selective agonist. Thus, dopamine D2 and/or D3 receptor agonists elicit emesis, while dopamine D1/D5 or D4 receptor-selective agonists are devoid of emetic properties.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Domperidone	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details
Haloperidol	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details