Other Phenothiazine Drugs

A considerable number of phenothiazine derivatives, varying in the side chain attached to the nitrogen and a substituent in the ring, have been introduced into clinical practice. The relationship between the chemical structure and the pharmacological activity of these drugs has been reviewed. 

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Triflupromazine hydrochloride, like other phenothiazine drugs exhibits fluorescence. This phenomenon was first explored in 0.2N sulfuric acid. The fluorescence peak was found in the range of 450 to 475 nm, shifting to slightly lower wavelength upon oxidation with potassium permanganate. As little as 0.01 to 0.05 [j,g of the pure substance per ml. of 0.2N sulfuric acid could be detected. Due to interference by other substances, the sensitivity in biological fluids was lower (about 0.8 i,g/ml of fluid). 

Mesoridazine acts analogous to other phenothiazine neuroleptics and is used for schizophrenia, behavioral problems, psychoneurotic displays, and in severe and chronic alcoholism. Synonyms of this drug are lidanil, serentil, and others. 

The piperidines, e.g. thioridazine, pipothiazine and pericyazine, have the lowest potential to cause extrapyramidal effects. Thioridazine is one of the most sedative phenothiazines. It may decrease the inotropic activity of digitalis by its quinidine-like action, which can cause myocardial depression, decreased efficiency of repolarization, and increased risk of tachyarrhythmias. With thioridazine drug induced sexual dysfunction and especially cardiotox-icity with prolongation of the QT-interval are more frequently seen than with other phenothiazines. For the above reasons thioridazine is withdrawn from the market in many countries. 

The determination of chlorpromazine and other phenothiazines with aqueous NaOH solution in a dimethylformamide medium has been successfully applied to their powder dosage forms [59]. The amperometric determination of chlorpromazine with Ce(S04)2 titrant was also described [60]. The drug was also determined by the titration with sodium lauryl sulfate in an imiscible phase [61]. 

The interactions of TDZ (6) with model membranes composed of different phospholipids were also studied by the same group [78]. Calorimetric studies demonstrated that TDZ (6) altered the thermotropic properties of negatively charged DMPC membranes to a larger extent than of zwitterionic phospholipids (PC and PE). The character of the drug-induced changes of the transition parameters of all studied lipids indicated that TDZ (6), similarly to other phenothiazine derivatives, was likely to be localized close to the po-lar/apolar interface of the bilayers. Experiments in which fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was employed revealed that TDZ (6) reduced the mobility of lipid molecules in a concentration-dependent manner and thus decreased membrane fluidity. The influence of TDZ (6) on isolated... 

TFP (5) was found to be a very effective blocker of human Kv2.1 potassium channels expressed in human glioblastoma cells [253]. As for other types of channels, for Kv2.1 the TFP-induced block was also dose-dependent (IC50 = 1.21 xM). Some of the other, non-phenothiazine drugs were even more effective blockers for the most potent, fluspirilene (an antipsychotic agent), substantial block was observed at 30 nM. 

With other phenothiazines (e.g., fluphen-azine with a piperazine side chain substituent), antagonism at other receptor types tends to recede into the background vis-a-vis the blockade of D2 dopamine receptors. In panel (B) on p. 235 the D2 receptor af nity of the drugs concerned is defined as ++, while the differences in absolute af nity for the other receptors are ignored. 

Debye-ScherrerX-ray diffraction photographs of phenothiazine and of some phenothiazine drugs were taken for analytical purposes by the Colleter group " and others. An exact knowledge of the molecular structure of phenothiazines may be useful to the under-... 

Sulfuric acid was often used, either alone or in conjunction with other oxidants such as ferric salts, to convert phenothiazine drugs and their metabolization products into the colored radical species, which may then be identified and estimated by spectrophotometry. Rieder found the absorption maximum of the... 

Phenothiazines do not produce analgesia but can potentiate the efficacy of other analgesic drugs, such as the opioids (p. 276). An exception to this is levomepromazine (methotrimeprazine), a phenothiazine used formerly in the horse in combination with the opioid etorphine (Petts Pleuvry 1983). Phenothiazines lower the MAC of inhalation anesthetics. In one controlled study, acepromazine was shown to decrease the MAC of halothane by approximately 37% (Doherty et al 1997b). 

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