Document Detail


Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight.
MedLine Citation:
PMID:  19935749     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The current set of studies describe the in vivo metabolic actions of the novel amylin-mimetic peptide davalintide (AC2307) in rodents and compares these effects with those of the native peptide. RESEARCH DESIGN AND METHODS: The anti-obesity effects of davalintide were examined after intraperitoneal injection or sustained peripheral infusion through subcutaneously implanted osmotic pumps. The effect of davalintide on food intake after lesioning of the area postrema (AP) and neuronal activation as measured by c-Fos, were also investigated. RESULTS: Similar to amylin, davalintide bound with high affinity to amylin, calcitonin and calcitonin gene-related peptide receptors. Acutely, davalintide displayed greater suppression of dark-cycle feeding and an extended duration of action compared with amylin (23 versus 6 h). Davalintide had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. Davalintide-induced weight loss through infusion was dose dependent, durable up to 8 weeks, fat-specific and lean-sparing, and was associated with a shift in food preference away from high-fat (palatable) chow. Metabolic rate was maintained during active weight loss. Both davalintide and amylin failed to suppress food intake after lesioning of the AP and activated similar brain nuclei, with davalintide displaying an extended duration of c-Fos expression compared with amylin (8 versus 2 h). CONCLUSION: Davalintide displayed enhanced in vivo metabolic activity over amylin while retaining the beneficial properties possessed by the native molecule. In vitro receptor binding, c-Fos expression and AP lesion studies suggest that the metabolic actions of davalintide and amylin occur through activation of similar neuronal pathways.
Authors:
C M Mack; C J Soares; J K Wilson; J R Athanacio; V F Turek; J L Trevaskis; J D Roth; P A Smith; B Gedulin; C M Jodka; B L Roland; S H Adams; A Lwin; J Herich; K D Laugero; C Vu; R Pittner; J R Paterniti; M Hanley; S Ghosh; D G Parkes
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Publication Detail:
Type:  Journal Article     Date:  2009-11-24
Journal Detail:
Title:  International journal of obesity (2005)     Volume:  34     ISSN:  1476-5497     ISO Abbreviation:  Int J Obes (Lond)     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-15     Completed Date:  2010-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101256108     Medline TA:  Int J Obes (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  385-95     Citation Subset:  IM    
Affiliation:
Amylin Pharmaceuticals, San Diego, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Amyloid / pharmacology*
Animals
Appetite Depressants / pharmacology*
Body Weight / drug effects*,  physiology
Dose-Response Relationship, Drug
Eating / drug effects*,  physiology
Energy Metabolism / drug effects,  physiology
Male
Peptides / pharmacology*
Rats
Rats, Sprague-Dawley
Satiety Response / drug effects*,  physiology
Weight Gain / drug effects*,  physiology
Chemical
Reg. No./Substance:
0/Amyloid; 0/Appetite Depressants; 0/Peptides; 0/davalintide; 106602-62-4/amylin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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