Phenothiazine dopamine receptor antagonists

Chlorpromazine is a phenothiazine with a large range of pharmacological actions it is a dopamine receptor antagonist, an alpha-adrenoceptor antagonist, a muscarinic antagonist, and an antihistamine. 

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. 

Dopamine-receptor antagonists having antipsychotic properties, such as phenothiazine, butyrophenone, and thioxanthene derivatives, and Gl-stimulant drugs, such as metoclopramide, are contraindicated with pergolide. The... 

It also seems plausible that antipsychotic drugs competitively bind with dopamine receptors and block the action of dopamine on corresponding receptor sites, thus lowering psychotic activity. Central dopamine receptors are subdivided into Dj, D2, and according to some sources, Dj receptors. These receptors have a high affinity for dopamine, but they differ in sensitivity to neuroleptics of various chemical classes. For example, drugs of the phenothiazine series are nonselective competitive Dj and D2 antagonists. Unlike phenoth-iazines, antipsychotics of the butyrophenone series such as haloperidol display selective action only on D2 receptors. 

In recent years traditional neuroleptics, as exemplified by chlorpromazine, have been structurally modified to produce drugs with greater affinity for dopamine receptors while retaining some of their activity on other receptor systems (e.g. on alpha] adrenoceptors, 5-HT2 receptors and histamine] receptors). In the non-phenothiazine series, a high degree of specificity for the D2 receptors has been achieved with sulpiride and pimozide, with haloperidol showing antagonistic effects on the 5-HT2 and alpha] adrenoceptors in addition to its selectivity for D2 receptors. The czs-(Z) isomers of the thioxanthines are potent neuroleptics that, in addition to... 

Both calmodulin and a calcium- and calmodulin-dependent phosphodiesterase activity occur in dispersed bovine parathyroid cells (20.). Some of the phenothiazines blocking the dopamine receptor in this tissue inhibit the interaction between calmodulin and the calmodulin-dependent phosphodiesterase. A series of experiments have tested the possibility that calmodulin might play a role in the effects of these agents on the parathyroid gland. The dopamine antagonists examined were weak inhibitors of calmodulin-stimulated phosphodiesterase activity (Table II). 

Phenothiazine derivatives are nonselective, competitive Dj and D2 antagonists that block dopamine activity on corresponding receptor sites. In addition, their action is... 

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