title: Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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: Amylin Pharmaceuticals, San Diego, CA, USA.
authors: C M
authors: CM
authors: Mack
authors: C J
authors: CJ
authors: Soares
authors: J K
authors: JK
authors: Wilson
authors: J R
authors: JR
authors: Athanacio
authors: V F
authors: VF
authors: Turek
authors: J L
authors: JL
authors: Trevaskis
authors: J D
authors: JD
authors: Roth
authors: P A
authors: PA
authors: Smith
authors: B
authors: B
authors: Gedulin
authors: C M
authors: CM
authors: Jodka
authors: B L
authors: BL
authors: Roland
authors: S H
authors: SH
authors: Adams
authors: A
authors: A
authors: Lwin
authors: J
authors: J
authors: Herich
authors: K D
authors: KD
authors: Laugero
authors: C
authors: C
authors: Vu
authors: R
authors: R
authors: Pittner
authors: J R
authors: JR
authors: Paterniti
authors: M
authors: M
authors: Hanley
authors: S
authors: S
authors: Ghosh
authors: D G
authors: DG
authors: Parkes
mesh_terms: D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D058228:Islet Amyloid Polypeptide; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000187:drug effects* / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D000682:Amyloid; D001067:Appetite Depressants; D058228:Islet Amyloid Polypeptide; D010455:Peptides; C553163:davalintide