| Histamine release and hypotensive reactions in dogs by solubilizing agents and fatty acids: analysis of various components in cremophor El and development of a compound with reduced toxicity. | |
| | |
MedLine Citation:
|
PMID: 6177219 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Anaphylactoid reactions in man following administration of drugs solubilized with cremophor El (polyethylenglycolglycerol riconoleate) are a considerable clinical problem. Since these reactions occur in dogs on first exposure and in pigs on second exposure, the 'dog model' was used in this communication to analyse components and chemical modifications of cremophor El and its components for their clinical effects, their hypotensive actions and their histamine-releasing capacity. Two series of experiments in 1978 and 1980 were performed in 144 adult mongrel dogs of both sexes. In these studies histamine release was not related to the effect of the solubilizing agents as tensides and was elicited by rather low doses (about 10--100 mg/kg i.v.). The effect of these substances on blood pressure and on blood histamine levels was connected with distinct chemical features: the most potent compounds were oxethylated and additionally esterified unsaturated or hydroxylated fatty acids. Several phases in hypotensive reactions were observed, including an immediate response, a delayed blood pressure response and a late response about 15--20 min after injection. Only the delayed response was associated with histamine release. The combination of cardiovascular effects and histamine release was fatal on some occasions indicating that histamine release can be dangerous. Compared to cremophor El, the tenside effect was equal, but the toxicity was reduced in oxethylated 12-hydroxystearic acid. It is recommended that this solubilizer should be used in further extended studies in animals and - if these are successful - in clinical trials. |
| | |
Authors:
|
W Lorenz; A Schmal; H Schult; S Lang; C Ohmann; D Weber; B Kapp; L Lüben; A Doenicke |
Related Documents
:
|
2831749 - Alpha-2-adrenoceptor function in alcohol withdrawal: a pilot study of the effects of iv... 2874899 - Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals. 7244749 - Effects of antihypertensive drug therapy on responses to isometric exercise. 16282369 - Clonidine-evoked respiratory effects in anaesthetized rats. 9352619 - Why is the hypotensive effect of clonidine greater in hypertensive rats? 2897989 - Desensitization of vascular and platelet alpha 2-adrenoceptors in rabbits with perineph... 11819019 - Distribution of patellofemoral joint pressures after femoral trochlear osteotomy. 22245299 - Pressure transmission through ureteric stents: a novel in vivo human study. 6469789 - Respiratory system, lung, and chest wall impedances in anesthetized dogs. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Agents and actions Volume: 12 ISSN: 0065-4299 ISO Abbreviation: Agents Actions Publication Date: 1982 Apr |
Date Detail:
|
Created Date: 1982-07-19 Completed Date: 1982-07-19 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0213341 Medline TA: Agents Actions Country: SWITZERLAND |
Other Details:
|
Languages: eng Pagination: 64-80 Citation Subset: IM |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blood Pressure / drug effects* Castor Oil / pharmacology Child Child, Preschool Dogs Fatty Acids / pharmacology* Female Glycerol / analogs & derivatives*, pharmacology, toxicity Histamine / blood Histamine Release / drug effects* Humans Infant Male Solvents / pharmacology*, toxicity Stearic Acids / pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Fatty Acids; 0/Solvents; 0/Stearic Acids; 51-45-6/Histamine; 56-81-5/Glycerol; 63393-92-0/cremophor EL; 8001-79-4/Castor Oil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Histamine release from human pulmonary mast cells.
Next Document: Species and tissue differences of histamine storage and release.