Chemical and toxicological studies on some phenothiazines

Phenothiazines are widely used in the treatment of certain psychiatric disorders. Overdoses of these drugs are common and are potentially lives threatening of patients. This work aims to study the chromatographic and spectrophotometric behavior of some of commonly used phenothiazines [chlorpromazine hydrochloride and fluphenazine decanoate]. And estimation of the drugs to determine their distribution among different tissues, hair and body fluids of albino rats by using quick, sensitive and reliable method of analysis. The present study was conducted on ninety albino rats. The study divided into two parts [A and B] each involved 45 rats; A: The chemical and toxicological studies on chlorpromazine hydrochloride in toxic, lethal and chronic toxic doses. B: The chemical and toxicological studies on fluphenazine decanoate in toxic, lethal and chronic toxic doses. After extraction of chlorpromazine and fluphenazine from brain, liver, kidney, muscle, hair and plasma with ammonium sulphate, identification of the drugs was done using color tests and thin layer chromatography. UV spectrophotomeric and HPLC analysis of the samples was done. The results revealed that thin-layer chromatography gave positive results with tissue extracts of all organs and in all doses. It was obvious from the obtained results that the method used for spectrophotometric analysis offers the advantages of simplicity, specificity without the need of further extraction or heating, besides having higher sensitivity range than most of the existing spectrophotometric methods. The highest concentration of chlorpromazine was found in the kidney in all doses, followed by serum in toxic dose and liver in both lethal and chronic toxicity. Then the distribution varies in the other organs according to the different doses. The mean concentration of chlorpromazine was higher with HPLC than that with spectrophotometric method with significant difference in all organs. The order of distribution of fluphenazine in various organs of animals receiving the toxic dose by both HPLC and spectrophotometric methods was; [kidney, muscles, serum, liver, lung, hair, brain and heart] While the order of distributions of fluphenazine in various organs of animals received the lethal dose by the two methods was; [kidney, liver, serum, muscle, brain, hair, heart and lung] and that for animals receiving the chronic toxic dose was,[kidney, liver, serum, muscle, hair, brain, lung and heart]. It was clear that the order of distributions of chlorpromazine and fluphenazine in various organs in all doses was the same either by spectrophotometric or by HPLC methods, but the concentration of the drug was higher by HPLC than that by spectrophotometer and this difference was significant in all organs

Evaluation of analgesic, antipyretic and anti-inflammatory activity of spirobarbitunylphenothiazines in rodents.

Analgesic, antipyretic and anti-inflammatory activities of newly synthesized spirobarbitunylphenothiazines viz 10-[7, 11-Di(4-4' dimethoxphenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5.5] undecane 1, 5 dione] acetylphenothiazine (test drug A) and 10-[7, 11-Di (N.N-dimethylaminophenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5, 5] undecane-1, 5 dione] acetylphenothiazine (test drug B) have been screened in Swiss mice and Wistar rats. The peripheral analgesic activity of test drugs A and B was investigated by acetic acid induced writhing test in Swiss mice while the central analgesic action was assessed by hot-wire (tail flick test) of the analgesiometer and tail-clip test in Wistar rats. Antipyretic activity was assessed on Brewer's yeast induced pyrexic model while antiinflammatory activity was seen on carrageenan induced hind paw oedema. Analgesic activity was found to be only of peripheral type as there was reduction of 66% in writhing responses by test drugs A and B in dose of 80 mg/kg in mice. No change in the tail flick responses was observed on analgesiometer or by tail clip by both the test drugs. Reduction of 1.5 to 2.0 degrees C in rectal temperature was observed in pyretic rats by test drugs A and B in dose of 80 mg/kg. 80% reduction in paw volume was noted in 80 mg/kg dose of both the test drugs which was comparable to the anti-inflammatory activity of 300 mg/kg, p.o. of phenylbutazone.

Proton magnetic resonance technique in determination of miquitazine

A new quantitative method for the determination of Mequitazine and its tablet form [primalan] [R] has been developed. The new method is based on comparison between the integral value of the doublet signal of the protons of the N-methylene at 10-position in Mequitazine and that singlet signal of the hexamine protons at 4.65 ppm. The new method is valuable for both powder and tablet forms, since it gives accurate and reproducible results