Promethazine enantiomers

Bosikova, Z., Klouhkova, 1., and Tesafova, E., Study of the stability of promethazine enantiomers by liquid chromatography using a vancomycin-bonded chiral stationary phase, J. Chromatogr. B, 770, 63, 2002. 

Various interesting biomedical applications of phenothiazines were investigated, such as the anti-inflammatory effects of fluphenazine and triflupro-mazine, the use of chloropromazine and trifluoperazine to determine the secondary and tertiary structure of haemoglobin and myoglobin, and the efficiency of the promethazine (+) enantiomer to inhibit the bone resorbing cells, which led to the development of new methods for the treatment of periodontitis and osteoporosis. Recently, it was shown that some phenothiazine derivatives inhibited the production of prions in cultured neuroblastoma cells, suggesting that these phenothiazines might be applied to treat CJD. 

Ponder, G.W. Stewart, J.T. A liquid chromatographic method for the determination of promethazine enantiomers in hunum wine and serum using solid-phase extraction and fluorescence detection. J.Pharm.BiomedAnal., 1995, 13, 1161-1166... 

The separation of promethazine enantiomers was developed by Zhu et al. [11] under the following conditions. 

Under established conditions good separation of promethazine enantiomers was achieved, Rp values were 0.80 and 0.89 and selectivity factor was a = 2.02. 

There are also known cases of drug enantiomers that possess completely different therapeutic properties. The (+)-2/ ,35 -stereoisomer of propoxyphene (dextropropoxyphene) is marketed as an analgesic agent, whereas its enantiomer ( )-(25, 3/ )-propoxyphene (levopropoxyphene) is available as an effective anti-tussive agent [3]. The enantiomers of some chiral drugs are known to possess essentially identical qualitative and quantitative pharmacological activities, for example, the antihistamine promethazine, which is marketed as a racemate [5]. 

Table 1 Binding Constants Between /3-CD and the Enantiomers of Promethazine Determined Using CE and NMR Spectroscopy... 

The enantiomers of promethazine have been resolved and have similar antihistaminic and other pharmacolcigical properties us described below. This is in conmi-st with resula of. studies of the phcniramincs and curbinoxamine compounds in which the chiral center is closer to the aromanc feature of the molecule. A.symmctry appears to have lesN intluencc on antihistaminic activity when the chiral center lies near the positively charged side-chain nitrogen. 

Ponder, G.W. Butram, S.L. Adams, A.G. Ramanathan, C.S. Stewart, J.T. Resolution of promethazine, ethopropazine, trimeprazine and trimipramine enantiomers on selected chiral stationary phases using high-performance liquid chromatography. J.Chromatogr.A, 1995, 692, 173-182... 

J. Lars G. Nilsson, J. Hermansson, et al.. Promethazine resolution, absolute configuration and direct chromatographic resolution of the enantiomers, Acta. Pharm. Suec., 21(1984)309. 

The formation of diastereomeric ureides from chloro-fomnate reagents has been used in quantitative assays and for the preparative separation of both secondary and tertiary amines. Quantitative assays for promethazine, a tertiary amine of the phenothiazine group of pharmaceuticals, have been developed. Maibaum [100] carried out a three-stage reaction in which the racemic promethazine was reacted with vinyl chloroformate and the carbamate was subsequently hydrolysed to the secondary amine. The enantiomeric ratio of the amine was then determined as the urea following reaction with a chiral isocyanate. In a later development, Witte et al. [lOI] directly derivatized the same compound with (— )-menthyl chloroformate (17) and separated the diastereomers by HPLC. (—)-Menthyl chloroformate has also been used to resolve the enantiomers of nomicotine as... 

Ponder et al. [739] studied the retention of promethazine, ethopropazine, trimeprazine, and trimipramine enantiomers on nine different chiral phases... 

---