MyJournals Home  

RSS FeedsToxins, Vol. 10, Pages 34: Azemiopsin, a Selective Peptide Antagonist of Muscle Nicotinic Acetylcholine Receptor: Preclinical Evaluation as a Local Muscle Relaxant (Toxins)

 
 

7 january 2018 13:01:22

 
Toxins, Vol. 10, Pages 34: Azemiopsin, a Selective Peptide Antagonist of Muscle Nicotinic Acetylcholine Receptor: Preclinical Evaluation as a Local Muscle Relaxant (Toxins)
 




Azemiopsin (Az), a linear peptide from the Azemiops feae viper venom, contains no disulfide bonds, is a high-affinity and selective inhibitor of nicotinic acetylcholine receptor (nAChR) of muscle type and may be considered as potentially applicable nondepolarizing muscle relaxant. In this study, we investigated its preclinical profile in regard to in vitro and in vivo efficacy, acute and chronic toxicity, pharmacokinetics, allergenic capacity, immunotoxicity and mutagenic potency. The peptide effectively inhibited (IC50 ~ 19 nM) calcium response of muscle nAChR evoked by 30 ?M (EC100) acetylcholine but was less potent (IC50 ~ 3 ?M) at ?7 nAChR activated by 10 ?M (EC50) acetylcholine and had a low affinity to ?4?2 and ?3-containing nAChR, as well as to GABAA or 5HT3 receptors. Its muscle relaxant effect was demonstrated at intramuscular injection to mice at doses of 30-300 g/kg, 30 g/kg being the initial effective dose and 90 g/kg--the average effective dose. The maximal muscle relaxant effect of Az was achieved in 10 min after the administration and elimination half-life of Az in mice was calculated as 20-40 min. The longest period of Az action observed at a dose of 300 g/kg was 55 min. The highest acute toxicity (LD50 510 ?g/kg) was observed at intravenous injection of Az, at intramuscular or intraperitoneal administration it was less toxic. The peptide showed practically no immunotoxic, allergenic or mutagenic capacity. Overall, the results demonstrate that Az has good drug-like properties for the application as local muscle relaxant and in its parameters, is not inferior to the relaxants currently used. However, some Az modification might be effective to extend its narrow therapeutic window, a typical characteristic and a weak point of all nondepolarizing myorelaxants.


Del.icio.us Digg Facebook Google StumbleUpon Twitter
 
71 viewsCategory: Toxicology
 
Toxins, Vol. 10, Pages 32: Development of a Deimmunized Bispecific Immunotoxin dDT2219 against B-Cell Malignancies (Toxins)
Toxins, Vol. 10, Pages 43: The Peptide PnPP-19, a Spider Toxin Derivative, Activates ?-Opioid Receptors and Modulates Calcium Channels (Toxins)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Toxicology

Use these buttons to bookmark us:
Del.icio.us Digg Facebook Google StumbleUpon Twitter


Valid HTML 4.01 Transitional
Copyright © 2008 - 2018 Indigonet Services B.V.. Contact: Tim Hulsen
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Travel Photos Nachrichten Indigonet Finances Leer Mandarijn
Indigonet Services BV is not responsible for any incorrect or outdated information on this site.
If, however, you would like to see an article removed, you can send us an e-mail quoting the article number.