Pramlintide

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Pramlintide
Systematic (IUPAC) name
?
Identifiers
CAS number	151126-32-8
ATC code	?
PubChem	16132446
Chemical data
Formula	C171H269N51O53S2
Mol. mass	3951.41 g/mol
Pharmacokinetic data
Bioavailability	30 to 40%
Protein binding	Approximately 60%
Metabolism	Renal
Half life	Approximately 48 minutes
Excretion	?
Therapeutic considerations
Pregnancy cat.	C(US)
Legal status	℞-only(US)
Routes	Subcutaneous

Pramlintide acetate (Symlin) is a relatively new adjunct treatment for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals.

Contents 1 Pharmacology 2 Approval 3 Design and structure 4 References 5 External links

[edit] Pharmacology

Pramlintide is an analogue of amylin, a small peptide hormone that is released into the bloodstream by the β-cells of the pancreas along with insulin, after a meal.^[1] Like insulin, amylin is deficient in individuals with diabetes.

By augmenting endogenous amylin, pramlintide aids in the absorption of glucose by slowing gastric emptying, promoting satiety via hypothalamic receptors (different receptors than for GLP-1), and inhibiting inappropriate secretion of glucagon, a catabolic hormone that opposes the effects of insulin and amylin.

[edit] Approval

Symlin has been approved for use by the FDA by type 1 and type 2 diabetics who use insulin.^[2] Symlin results in weight loss, allows patients to use less insulin, lowers average blood sugar levels, and substantially reduces what otherwise would be a large unhealthy rise in blood sugar that occurs in diabetics right after eating. Symlin is the only drug approved by the FDA to lower blood sugar in type 1 diabetics since insulin's discovery in the early 1920s.

[edit] Design and structure

Since native human amylin is highly amyloidogenic and potentially toxic, the strategy for designing pramlintide was to substitute residues from rat amylin, which is not amyloidogenic (but would presumably retain clinical activity). Proline residues are known to be structure-breaking residues, so these were directly grafted into the human sequence. The glutamine residue was also substituted with an asparagine, probably because glutamines are generally considered to be amyloid-promoting.

Amino acid sequences:

Pramlintide: KCNTATCATNRLANFLVHSSNNFGPILPPTNVGSNTY-(NH2)
Amylin:      KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-(NH2)
Rat amylin:  KCNTATCATQRLANFLVRSSNNFGPVLPPTNVGSNTY-(NH2)


Pramlintide (positively charged) is delivered as an acetate salt.

[edit] References

1. ^ Jones MC (2007). "Therapies for diabetes: pramlintide and exenatide". American family physician 75 (12): 1831–5. PMID 17619527. 
2. ^ Ryan GJ, Jobe LJ, Martin R (2005). "Pramlintide in the treatment of type 1 and type 2 diabetes mellitus". Clinical therapeutics 27 (10): 1500–12. doi:10.1016/j.clinthera.2005.10.009. PMID 16330288. 

[edit] External links

• www.symlin.com - product website
• www.amylin.com - Symlin page on the Amylin Pharmaceuticals website
  

v • d • e Oral antidiabetic drugs and Insulin analogs (A10) Biguanides Metformin Sulfonylureas Carbutamide, Chlorpropamide, Glibenclamide (Glyburide), Gliclazide, Glimepiride, Glipizide, Gliquidone, Tolazamide, Tolbutamide Alpha-glucosidase inhibitors Acarbose, Miglitol, Voglibose Thiazolidinediones (TZD) Pioglitazone, Rivoglitazone†, Rosiglitazone, Troglitazone‡ Meglitinides Nateglinide, Repaglinide, Mitiglinide Dipeptidyl peptidase-4 (DPP-4) inhibitors Alogliptin†, Saxagliptin†, Sitagliptin, Vildagliptin Glucagon-like peptide-1 analog Exenatide, Liraglutide†, Albiglutide† Amylin analog Pramlintide Insulin analogs fast acting (Insulin lispro, Insulin aspart, Insulin glulisine), long acting (Insulin glargine, Insulin detemir), Inhalable insulin (Exubera) Dual PPAR agonists Aleglitazar†, Muraglitazar§, Tesaglitazar§ SGLT2 inhibitor Dapagliflozin†, Remogliflozin† †Undergoing clinical trials. ‡ Withdrawn from market. §Development halted.