ABSTRACT
1. The potential effects of new drugs on the digestive system can be examined in a number of model systems of which intestinal motility in the mouse and/or gastric emptying in the rat are examples recommended for safety pharmacology evaluation. 2. Intestinal motility, assessed by the transit of carmine dye in the mouse and gastric motility, assessed by stomach weight in the rat, were examined using a range of clinical drugs or potent pharmacological agents known to affect gastrointestinal function. Assessment of both models in the guinea-pig was also evaluated. 3. Activity was demonstrated with codeine, diazepam, atropine and CCK-8 (all of which inhibited gastric function). However, neither model gave consistent and reliable results with the remaining reference compounds, namely metoclopramide, bethanechol, cisapride, deoxycholate, carbachol and domperidone. 4. In conclusion, this investigation questions the usefulness of simple models of gastrointestinal transport in the rodent as a means of detecting potential effects of a new drug on the digestive system. This finding should be of concern to the pharmaceutical industry as these simple models are routinely used as part of a regulatory safety pharmacology 'package' of studies.
Subject(s)
Gastric Emptying/drug effects , Gastrointestinal Motility/drug effects , Pharmacology/methods , Animals , Female , Guinea Pigs , Male , Mice , Mice, Inbred ICR , Rats , Rats, Sprague-Dawley , Toxicology/methodsABSTRACT
Despite an increased understanding of the potential dangers of benzodiazepines among doctors and patients, and a decline in anxiolytic prescribing, motivating and supporting current benzodiazepine users through withdrawal can be difficult and time consuming for medical services. Self-help organisations offer another approach. This is a study of one such organisation, TRANX (UK), which examined the characteristics of its members and their outcome. The results suggest that this organisation did provide effective counselling and support for its members, and implies that self-help is a realistic alternative or adjunct to orthodox health care for those wishing to withdraw from benzodiazepines.
Subject(s)
Anti-Anxiety Agents/adverse effects , Self-Help Groups , Substance Withdrawal Syndrome/rehabilitation , Substance-Related Disorders/rehabilitation , Adult , Diazepam/adverse effects , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , London , Male , Middle Aged , Substance Withdrawal Syndrome/psychology , Substance-Related Disorders/psychologySubject(s)
Feeding and Eating Disorders/complications , Trichotillomania/etiology , Body Image , Body Weight , Female , Humans , Sex FactorsSubject(s)
Anorexia Nervosa/therapy , Eating , Hospitalization , Anorexia Nervosa/psychology , Female , Humans , Patient Compliance/psychologyABSTRACT
An increasing concern over the LD50 study has become apparent over the years and even more so recently in Britain with the Home Office Publication on the subject and comments and opinions expressed in the National Press. Particularly with respect to the Pharmaceutical and Agrochemical Industries, the number of animals used depends on the number required to satisfy the Regulatory Authorities. Is there a scientific rationale for using the number of animals required? Data is presented justifying the use of smaller numbers of animals for establishing the acute toxicity of a chemical.
Subject(s)
Lethal Dose 50 , Statistics as Topic , Animals , Sex Factors , Toxicology/standardsABSTRACT
FPL 55712, previously reported to be a selective antagonist of SRS-A on the guinea-pig ileum, has now been shown to be similarly selective, though less potent, in its antagonism of contractions induced by SRS-A on in vitro preparations of respiratory smooth muscle (human bronchial strips and guinea-pig tracheal tubes). In vivo, bronchoconstriction induced in guinea-pigs by the endogenous release of SRS-A was partially inhibited by relatively large intravenous doses of FPL 55712 and by inhalation of aerosol compound. FPL 55712 was very rapidly cleared following intravenous administration.
Subject(s)
Chromones/pharmacology , SRS-A/antagonists & inhibitors , Animals , Bronchi/immunology , Constriction, Pathologic/immunology , Guinea Pigs , Half-Life , Humans , Ileum/immunology , Trachea/immunologySubject(s)
Benzopyrans/pharmacology , SRS-A/antagonists & inhibitors , Acetylcholine/antagonists & inhibitors , Animals , Biological Assay , Dose-Response Relationship, Drug , Ethers/pharmacology , Guinea Pigs , Histamine H1 Antagonists/pharmacology , Humans , Ileum/drug effects , Muscle Contraction/drug effects , Phenols/pharmacology , Prostaglandin Antagonists , Rats , SRS-A/pharmacology , Serotonin Antagonists , Species SpecificityABSTRACT
1. An automatic method for doing assays on superfused isolated tissues has been developed using the Autoanalyser sample turntable.2. Responses in the range used for assays are independent of the preceding responses when elicited at 1 min intervals. A longer interval was found to be necessary when using the conventional immersion method.3. The index of precision was similar to that reported for other superfusion methods.4. The assay method behaved as though it were assaying histamine selectively in two samples of material released by the anaphylactic reaction of passively sensitized guinea-pig lung. Responses to anaphylactically released material were also independent of the preceding response at 1 min intervals.5. Some theoretical considerations are discussed concerning the arrangement of doses, and the interpolation of results, in 2 + 1 dose assays. The object was to maximize speed while still allowing a valid estimate of the potency and its error.
