The structures of the phenothiazine derivatives described later are given in Table 12.3.
Chlorpromazine Hydrochloride, USP. Chlorpromazine hydrochloride, 2-chloro- 10-[3-(dimethylamino)propyl]phe-
nothiazine monohydrochloride (Thorazine), was the first phe-nothiazine compound introduced into therapy. It is still useful as an antipsychotic. Other uses are in nausea, vomiting, and hiccough. Oral doses of chlorpromazine and thioridazine have systemic availability of 25% to 35% because of significant first-pass metabolism. Chlorpromazine and other pheno-thiazines are metabolized extensively by CYP2D6 (Fig. 12.6). In contrast, bioavailability of chlorpromazine may be increased up to 10-fold with injections, but the clinical dose usually is decreased by only threefold to fourfold. Chlorpromazine may weakly induce its own hepatic metabolism, because its concentration in blood is lower after several weeks of treatment at the same dosage. Alterations of GI motility also may contribute. The drug has significant sedative and hypotensive properties, possibly reflecting central histaminergic and peripheral ^-noradrenergic blocking activity, respectively. Effects of peripheral anticholinergic activity are common. As with the other phenothiazines, the effects of other CNS-depressant drugs, such as sedatives and anesthetics, can be potentiated.
TABLE 12.3 Phenothiazine Derivatives
Generic Name Proprietary Name
Propyl Dialkylamino Side Chain
Promazine hydrochloride, USP Sparine
Chlorpromazine hydrochloride, USP
Thorazine Triflupromazine hydrochloride, USP Vesprin
Akyl Piperidyl Side Chain
Thioridazine hydrochloride, USP Mellaril
Mesoridazine besylate, USP Serentil
Propyl Piperazine Side Chain
Prochlorperazine maleate, USP Compazine
H Cl CF3
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