DT-Web

DB01278 - Pramlintide


Identification
Name Pramlintide
Accession Number DB01278
Type biotech
Description Pramlintide is a relatively new adjunct treatment for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone that is released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 3949.3896
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy.
Mechanism of action Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3.
Absorption The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%.
Protein binding Pramlintide does not extensively bind to blood cells or albumin (approximately 40% of the drug is unbound in plasma).
Biotransformation Metabolized primarily by the kidneys.
Route of elimination Pramlintide is metabolized primarily by the kidneys.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Aclidinium May increase the risk of inhibition of GI motility via pharmacodynamic synergism. Consider alternate therapy.
Carbinoxamine Pramlintide may enhance the anticholinergic effect of Anticholinergics such as carbinoxamine. These effects are specific to the gastrointestinal tract. Use caution during concomitant therapy with pramlintide and anticholinergics. Additive effects on reduced gastrointestinal motility may occur.
Clidinium Pramlintide may enhance the anticholinergic effect of anticholinergics such as clidinium. These effects are specific to the GI tract. Use caution during concomitant therapy with pramlintide and anticholinergics. Additive effects on reduced GI motility may occur.
Doxylamine May cause additive slowing of GI motility.
Insulin Lispro Concomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
Thiothixene The anticholinergic effects of Tranylcypromine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Tiotropium The anticholinergic effects of Tiotropium may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Tolterodine Additive reduction in gut motility may occur. Consider alternate therapy or use caution during concomitant therapy.
Tranylcypromine The anticholinergic effects of Tranylcypromine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Trihexyphenidyl The anticholinergic effects of Trihexyphenidyl may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Trimeprazine The anticholinergic effects of Trimeprazine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Trimethobenzamide The anticholinergic effects of Trimethobenzamide may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Trimipramine The anticholinergic effects of Trimipramine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Triprolidine The anticholinergic effects of Triprolidine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Trospium The anticholinergic effects of Trospium may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Zuclopenthixol May cause additive reduction in GI motility. Use caution or consider alternate therapy.
Food Interactions Not Available

Targets


Calcitonin receptor
Name Calcitonin receptor
Gene Name CALCR
Pharmacological action yes
Actions agonist
References
  • Nyholm B, Brock B, Orskov L, Schmitz O: Amylin receptor agonists: a novel pharmacological approach in the management of insulin-treated diabetes mellitus. Expert Opin Investig Drugs. 2001 Sep;10(9):1641-52. - Pubmed
  • Roth JD, Maier H, Chen S, Roland BL: Implications of amylin receptor agonism: integrated neurohormonal mechanisms and therapeutic applications. Arch Neurol. 2009 Mar;66(3):306-10. - Pubmed
  • Lutz TA: The role of amylin in the control of energy homeostasis. Am J Physiol Regul Integr Comp Physiol. 2010 Jun;298(6):R1475-84. Epub 2010 Mar 31. - Pubmed
  • Qi T, Hay DL: Structure-function relationships of the N-terminus of receptor activity-modifying proteins. Br J Pharmacol. 2010 Mar;159(5):1059-68. Epub 2009 Dec 10. - Pubmed
  • Qi T, Christopoulos G, Bailey RJ, Christopoulos A, Sexton PM, Hay DL: Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Mol Pharmacol. 2008 Oct;74(4):1059-71. Epub 2008 Jul 1. - Pubmed
  • Hay DL, Christopoulos G, Christopoulos A, Sexton PM: Amylin receptors: molecular composition and pharmacology. Biochem Soc Trans. 2004 Nov;32(Pt 5):865-7. - Pubmed
DTHybrid score 2.3626
Receptor activity-modifying protein 1
Name Receptor activity-modifying protein 1
Gene Name RAMP1
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Nyholm B, Brock B, Orskov L, Schmitz O: Amylin receptor agonists: a novel pharmacological approach in the management of insulin-treated diabetes mellitus. Expert Opin Investig Drugs. 2001 Sep;10(9):1641-52. - Pubmed
  • Roth JD, Maier H, Chen S, Roland BL: Implications of amylin receptor agonism: integrated neurohormonal mechanisms and therapeutic applications. Arch Neurol. 2009 Mar;66(3):306-10. - Pubmed
  • Lutz TA: The role of amylin in the control of energy homeostasis. Am J Physiol Regul Integr Comp Physiol. 2010 Jun;298(6):R1475-84. Epub 2010 Mar 31. - Pubmed
  • Qi T, Hay DL: Structure-function relationships of the N-terminus of receptor activity-modifying proteins. Br J Pharmacol. 2010 Mar;159(5):1059-68. Epub 2009 Dec 10. - Pubmed
  • Qi T, Christopoulos G, Bailey RJ, Christopoulos A, Sexton PM, Hay DL: Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Mol Pharmacol. 2008 Oct;74(4):1059-71. Epub 2008 Jul 1. - Pubmed
  • Hay DL, Christopoulos G, Christopoulos A, Sexton PM: Amylin receptors: molecular composition and pharmacology. Biochem Soc Trans. 2004 Nov;32(Pt 5):865-7. - Pubmed
DTHybrid score 1.6002
Receptor activity-modifying protein 2
Name Receptor activity-modifying protein 2
Gene Name RAMP2
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Roth JD, Maier H, Chen S, Roland BL: Implications of amylin receptor agonism: integrated neurohormonal mechanisms and therapeutic applications. Arch Neurol. 2009 Mar;66(3):306-10. - Pubmed
  • Qi T, Hay DL: Structure-function relationships of the N-terminus of receptor activity-modifying proteins. Br J Pharmacol. 2010 Mar;159(5):1059-68. Epub 2009 Dec 10. - Pubmed
  • Qi T, Christopoulos G, Bailey RJ, Christopoulos A, Sexton PM, Hay DL: Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Mol Pharmacol. 2008 Oct;74(4):1059-71. Epub 2008 Jul 1. - Pubmed
  • Hay DL, Christopoulos G, Christopoulos A, Sexton PM: Amylin receptors: molecular composition and pharmacology. Biochem Soc Trans. 2004 Nov;32(Pt 5):865-7. - Pubmed
DTHybrid score 1.6
Receptor activity-modifying protein 3
Name Receptor activity-modifying protein 3
Gene Name RAMP3
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Nyholm B, Brock B, Orskov L, Schmitz O: Amylin receptor agonists: a novel pharmacological approach in the management of insulin-treated diabetes mellitus. Expert Opin Investig Drugs. 2001 Sep;10(9):1641-52. - Pubmed
  • Roth JD, Maier H, Chen S, Roland BL: Implications of amylin receptor agonism: integrated neurohormonal mechanisms and therapeutic applications. Arch Neurol. 2009 Mar;66(3):306-10. - Pubmed
  • Lutz TA: The role of amylin in the control of energy homeostasis. Am J Physiol Regul Integr Comp Physiol. 2010 Jun;298(6):R1475-84. Epub 2010 Mar 31. - Pubmed
  • Qi T, Hay DL: Structure-function relationships of the N-terminus of receptor activity-modifying proteins. Br J Pharmacol. 2010 Mar;159(5):1059-68. Epub 2009 Dec 10. - Pubmed
  • Qi T, Christopoulos G, Bailey RJ, Christopoulos A, Sexton PM, Hay DL: Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Mol Pharmacol. 2008 Oct;74(4):1059-71. Epub 2008 Jul 1. - Pubmed
  • Hay DL, Christopoulos G, Christopoulos A, Sexton PM: Amylin receptors: molecular composition and pharmacology. Biochem Soc Trans. 2004 Nov;32(Pt 5):865-7. - Pubmed
DTHybrid score 1.6012

Predictions


Id Partner name Gene Name Score
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