Interaction of trimeprazine with cyclodextrins in aqueous solution.
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The synergistic effect of pH and complexation with cyclodextrins on some properties of phenothiazine derivative--trimeprazine (TM) was investigated. Inclusion complexes of TM with beta-cyclodextrin (beta-CD) and its substituted derivatives (DM-beta-CD, HP-beta-CD, beta-CDsulf) were obtained in phosphate buffer solution of different pH (6.8; 5.9; 5.0) using spectral and phase solubility methods Irrespective of the method of determination the apparent stability constant of TM-beta-CD system was the greatest and, in the case of the spectral method, its value increased with decreasing pH. The results obtained by the method of solubility diagrams indicate that increase in solubility of the basic form of TM, following decrease of pH, resulted rather from its transformation to a better soluble, protonated form than its inclusion into CD cavity. The thermodynamic parameters estimated from linear Van't Hoff plot suggest that the van der Waals forces were operating in the TM-beta-CD system. The effect of pH and the presence of cyclodextrins on photostability of TM was also investigated. The photochemical decomposition of TM in the absence and in the presence of CD proceeds according to the first order reaction. The charged form of TM was more stable than free base of this drug and hence the stability of TM increases first of all as result of a decrease in pH and then owing to the presence of CD. The data of 13C NMR analysis indicate that the aromatic portion of TM molecule tends to the interior of CD. (+info)
THE EFFECT OF SOME NEW ANTIHISTAMINES ON THE ANAPHYLACTIC MICROSHOCK OF THE GUINEA-PIG.
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The dose/response curves for the protective effects of the new antihistamine compounds trimeprazine, 10-(3-diethylamino-2-methylpropyl)phenothiazine 1,1-dioxide hydrochloride (oxomemazine hydrochloride), cyproheptadine, homochlorcyclizine and methotrimeprazine against the anaphylactic microshock of the guinea-pig were similar to that of promethazine. The first three compounds, however, protected at lower doses than promethazine (5 to 10 mug/kg). The protective effect of cyproheptadine lasted longer than 24 hr. (+info)
Determination of trimeprazine-facilitated sedation in children by hair analysis.
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Trimeprazine or alimemazine is largely used as an antipruritic agent, but it is also used for insomnia, cough, and oral premedication in pediatric day surgery. The first cases involving repetitive sedation linked to the use of trimeprazine as a drug-facilitated crime and subsequent impairment of two children are reported. Because of the long delay between the alleged crime and clinical examination, collection of blood or urine was of little value. This is the reason why the laboratory developed an original approach based on hair testing by liquid chromatography-tandem mass spectrometry. A strand of hair from each child was sampled about 2 months after the first suspicion of administration and was cut into small segments. After cutting into small pieces, 20 mg of hair was incubated overnight in a phosphate buffer (pH 8.4). The aqueous phase was extracted by 5 mL of a mixture of diethyl ether/methylene chloride (80:20) in presence of diazepam-d(5) used as the internal standard (IS). Hair extract was separated on a XTerra MS C18 column using a gradient of acetonitrile and formate buffer. Detection was based on two daughter ions: transitions m/z 299.3 to 299.0 and 100.0 and m/z 289.9 to 154.0 for trimeprazine and the IS, respectively. In the hair of the two subjects, trimeprazine was detected at concentrations in the range 23 to 339 pg/mg. The stepmother, who was the perpetrator in both cases, did not challenge the use of trimeprazine as a sedative drug. (+info)
Controlled trial of trimeprazine tartrate for night waking.
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Mild hypnotics are often recommended for young children with sleep problems. This study assesses the efficacy of trimeprazine tartrate in 1 to 3 year old children with persistent and severe night waking in a double blind crossover trial with placebo. Children on treatment with trimeprazine had significantly fewer wakings, less time awake at night, and more night time sleep compared with those on treatment with placebo. There were no differences in these sleep variables when the first and last (fourth) week of treatment with drugs were compared. Follow up observations showed no significant difference in any sleep variables from baseline measures. The results are consistent with the idea that trimeprazine tartrate may be a useful short term treatment for night waking in young children. (+info)
Mechanism of action of antipruritic drugs.
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Astemizole and terfenadine, two potent non-sedative H1 antihistamines, had no effect on itch measured objectively as nocturnal scratching and subjectively on a 10 cm line. Trimeprazine, however, a more sedative but less potent H1 antihistamine, was antipruritic, as was nitrazepam, a sedative benzodiazepine. We concluded (a) that antipruritic drugs act centrally by a property related to sedation; (b) H1 receptor antagonists have a peripheral antipruritic action only when itch is due to histamine release, as in the wealing disorders. Thus the new nonsedative H1 antihistamines have no place in the treatment of itch from other causes. (+info)
Phenothiazine-induced increase in thyroid autoantigens and costimulatory molecules on thyroid cells: a pathophysiological mechanism for drug-induced autoimmunity?
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We have previously demonstrated (J Immunol 1995; 154:3593) that MHC class II antigens can be induced on thyroid epithelial cells (TEC) by alimemazine, a member of the phenothiazine group. Although this expression of MHC class II antigens on TEC confers the theoretical ability to behave as antigen-presenting cells (APC), the simultaneous expression of self antigens and co-receptor(s) must also occur for efficient presentation of self antigens. Therefore, we investigated whether alimemazine applied at pharmacologic doses would modify the expression of thyroid antigens, and simultaneously, the expression of intercellular adhesion molecule-1 (ICAM-1), B7, and LFA-1 co-receptors in human TEC in culture. Using polymerase chain reaction (PCR) amplification and Northern blot analysis, we showed that alimemazine induces increases in thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) cDNA, within the first 2 h following its addition. This phenomenon is followed 48 h later by an increase of Tg and TSH-R protein expression on the surface of TEC. Furthermore, increases in the expression of ICAM-1 and B7 co-receptors were concomitantly observed. These results suggest that alimemazine, a drug currently used in paediatrics, could play a role in the induction and perpetuation of thyroid autoimmune disorders by transforming TEC into functional APC. (+info)
A double blind randomized comparison of oral trimeprazine-methadone and ketamine-midazolam for sedation of pediatric dental patients for oral surgical procedures.
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The safety and efficacy of an oral sedation technique for children having minor oral surgical procedures under local anesthesia were studied. One hundred healthy children between the ages of 2 and 7 yr received either a combination of midazolam (0.35 mg/kg) and ketamine (5 mg/kg) (Group A), or a combination of trimeprazine (3 mg/kg) and methadone (0.2 mg/kg) (Group B) 30 min preoperatively. Hemodynamic parameters, adverse reactions, postoperative recovery, and behavior were evaluated. More children were asleep, but rousable to verbal commands, 30 min after drug administration in Group A (40%) than in Group B (8%). Immediately before the dental procedure, 46% of children in Group A were asleep in contrast to 8% of children in group B. Significantly more children in Group A were awake, coughing, crying, and moving purposefully 30 and 60 min after admission to the recovery room. Two children (4%) in Group A vomited. Ten (20%) children in Group A hallucinated compared to none in Group B. The surgeon rated the procedure as good or very good in 94% of children in Group A compared to 78% in Group B. Our results show that the combination of midazolam and ketamine, administered orally, is a safe, effective, and practical approach to managing children for minor oral surgical procedures under local anesthesia. (+info)