ABSTRACT
The cytostatic/cytotoxic effects of the maleimide derivative 1-(4-Cl-Benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) have been estimated on epithelial derived human cell cultures (Colo 205, MCF-7, and Hela). The anticancer and toxic effects of MI-1 have been investigated on DMH-induced cancer development and normal colon morphology in rats. The results showed that the compound studied has low cytotoxicity but produces a strong antiproliferative effect on cell cultures and partially suppresses colon cancer development in DMH-induced model. The MI-1 effect on normal colon mucosa is insignificant, and no destructive changes have been detected in the intestine of rats. This maleimide derivate can be considered as a promising anticancer drug.
Subject(s)
Aniline Compounds/pharmacology , Antineoplastic Agents/pharmacology , Colonic Neoplasms/drug therapy , Cytotoxins/pharmacology , Linoleic Acids/pharmacology , Maleimides/pharmacology , Polyunsaturated Alkamides/pharmacology , Pyrroles/pharmacology , Aniline Compounds/chemistry , Animals , Antineoplastic Agents/chemistry , Colonic Neoplasms/chemically induced , Colonic Neoplasms/pathology , Cytotoxins/chemistry , Dimenhydrinate/toxicity , Drug Screening Assays, Antitumor , Humans , Linoleic Acids/chemistry , Male , Maleimides/chemistry , Polyunsaturated Alkamides/chemistry , Pyrroles/chemistry , RatsABSTRACT
HISTORY: A 13-month-old girl suffered from 3 generalized tonic-clonic seizures for several minutes within a total period of 9 hours. History revealed that the child received a total of 5 dimenhydrinate containing suppositories à 40 mg during the previous 2 days (i. e. 23 mg dimenhydrinate per kg body weight) due to enteritis with vomiting. The first seizure occurred 10 hours after the last administration. INVESTIGATIONS: The plasma level of diphenhydramin was 230 µg/l approximately one hour after the first seizure. Electroencephalography showed no pathological signs, an MRI scan of the brain was normal except of several small gliotic spots and body temperature was regularly. TREATMENT AND COURSE: Two stationary occurring seizures were stopped with 5 mg diazepam rectally. Continued surveillance and an EEG two days later showed age-appropriate normal findings. There were no further seizures in the next 4 years. CONCLUSION: Infants have the risk to develop dimenhydrinate intoxication, especially in cases where suppositories were given repeatedly because of intermittent defecation.
Subject(s)
Antiemetics/toxicity , Dimenhydrinate/toxicity , Drug Overdose/diagnosis , Epilepsy, Tonic-Clonic/chemically induced , Gastroenteritis/drug therapy , Antiemetics/administration & dosage , Dimenhydrinate/administration & dosage , Dose-Response Relationship, Drug , Drug Administration Schedule , Electroencephalography/drug effects , Female , Follow-Up Studies , Humans , Infant , SuppositoriesABSTRACT
In this study, we aimed to investigate and compare the direct toxic and teratogenic effects of dimenhydrinate, metoclopramide and trimethobenzamide HCl, antiemetic drugs on embryonic growth and development in cultured rat embryos. Embryos were explanted on day 9.5 of gestation and cultured. Whole rat serum was used as a culture medium for the control group while different concentrations of dimenhydrinate (2.5-20 µg/ml), metoclopramide (10-50 µg/ml) and trimethobenzamide HCl (25-100 µg/ml) were added to serum for the experimental groups. Effects of antiemetics on embryonic developmental parameters were compared, and embryos were evaluated for the presence of any malformations. Also, the total DNA was extracted from the cells to determine the fragmentation of nuclear DNA of embryonic cells. Compared with the control embryos, the antiemetics significantly decreased all growth and developmental parameters dose dependently. There was no difference regarding the fragmentation of nuclear DNA of the all used agents and controls. Amongst the agents, trimethobenzamide HCl was found to have more toxic and teratogenic potential, and metoclopramide appears to be the least toxic antiemetic and therefore could be more safely used and might be preferred for the treatment of nausea and vomiting in pregnancy.
Subject(s)
Antiemetics/toxicity , Benzamides/toxicity , Dimenhydrinate/toxicity , Embryo, Mammalian/drug effects , Embryonic Development/drug effects , Metoclopramide/toxicity , Animals , Embryo Culture Techniques , Mutagenicity Tests , RatsABSTRACT
Antiemetics are widely used drugs, frequently administered to alleviate postoperative and postchemotherapeutic nausea and vomiting. While antiemetics do not induce peripheral neurotoxicity when administered systemically, it is not known whether peripheral nerve injury can occur as a result of inadvertent intraneural injection during intramuscular administration. The purpose of this study was to characterize the neurotoxic effect of three commonly used antiemetic agents (promethazine, dimenhydrinate, and prochlorperazine) as compared to saline in the rat sciatic nerve model. Intrafascicular and extrafascicular injection as well as direct application of the antiemetic drugs were performed. Nerves were harvested at 2 weeks postoperatively for histology and morphometry, with an additional sacrifice point at 8 weeks for the intrafascicular injection group. Injection injuries caused by antiemetic drugs differed depending on the agent injected and the location of injection. Extrafascicular injection and direct application caused no damage. Intrafascicular injection caused diffuse axonal injury in the promethazine and dimenhydrinate groups, while prochlorperazine caused only focal injury. Regeneration was prominent at 8 weeks in all intrafascicular injection groups in this rat model. Prochlorperazine thus appears to be less neurotoxic when injected intraneurally and should preferentially be used for intramuscular injections.
