Chemistry:Pramlintide
 Golden line indicates disulfide bond | |
| Clinical data | |
|---|---|
| Trade names | Symlin |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a605031 |
| Pregnancy category |
|
| Routes of administration | Subcutaneous |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | 30 to 40% |
| Protein binding | ~60% |
| Metabolism | Renal |
| Elimination half-life | ~48 minutes |
| Identifiers | |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C171H267N51O53S2 |
| Molar mass | 3949.44 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
  (what is this?) (verify) | |
Pramlintide (trade name Symlin) is an injectable amylin analogue drug for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca).[1] Pramlintide is sold as an acetate salt.
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.[2] Like insulin, amylin is completely absent in individuals with Type I diabetes.[3]
In synergy with endogenous amylin, pramlintide aids in the regulation of blood 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. Pramlintide also has effects in raising the acute first-phase insulin response threshold following a meal.[citation needed]
Both a reduction in glycated hemoglobin and weight loss have been shown in insulin-treated patients with type 2 diabetes taking pramlintide as an adjunctive therapy.[4]
Research Applications
In the research field, pramlintide has been experimented with and used as a potential treatment drug. Pramlintide has demonstrated its ability to decrease amyloid beta plaques in Alzheimer's disease mouse models.[5]
Approval
Pramlintide has been approved on 3/16/2005 by the FDA, for use by type 1 and type 2 diabetic patients who use insulin.[6](Subscription content?) Pramlintide 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.
Apart from insulin analogs, pramlintide is the only drug approved by the FDA to lower blood sugar in type 1 diabetics since insulin in the early 1920s.[citation needed][7]
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 less amyloidogenic[8][9] but presumably retains clinical activity. Proline residues are known to be structure-breaking[clarification needed] residues, so these were directly grafted into the human sequence. Despite its enhanced stability compared to human amylin, however, pramlintide is still able to organize into amyloid material.[10]
Amino acid sequences:
| Pramlintide | KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-(NH2)
|
| Amylin | KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-(NH2)
|
| Rat amylin | KCNTATCATQRLANFLVRSSNNLGPVLPPTNVGSNTY-(NH2)
|
Pramlintide is a positively charged protein.[citation needed]
References
- ↑ "AstraZeneca buys BMS out of diabetes alliance". 19 December 2013. http://www.pmlive.com/pharma_news/astrazeneca_buys_bms_out_of_diabetes_alliance_528427.
- ↑ "Therapies for diabetes: pramlintide and exenatide". American Family Physician 75 (12): 1831–1835. June 2007. PMID 17619527. http://www.aafp.org/afp/2007/0615/p1831.pdf.
- ↑ "Pramlintide in the treatment of diabetes mellitus". BioDrugs 22 (6): 375–386. 2008. doi:10.2165/0063030-200822060-00004. PMID 18998755.
- ↑ "Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients". Obesity Research 12 (4): 661–668. April 2004. doi:10.1038/oby.2004.76. PMID 15090634.
- ↑ "Pramlintide: The Effects of a Single Drug Injection on Blood Phosphatidylcholine Profile for Alzheimer's Disease". Journal of Alzheimer's Disease 62 (2): 597–609. 2018. doi:10.3233/jad-170948. PMID 29480193.
- ↑ "Pramlintide in the treatment of type 1 and type 2 diabetes mellitus". Clinical Therapeutics 27 (10): 1500–1512. October 2005. doi:10.1016/j.clinthera.2005.10.009. PMID 16330288.
- ↑ "Dual-Hormone, Artificial Pancreas with Insulin and Pramlintide Significantly Improves Glucose Levels, Compared to Insulin-Only Artificial Pancreas" (in en). http://www.diabetes.org/newsroom/press-releases/2018/dual-hormone-artificial-pancreas-insulin-pramlintide-improves-glucose.html.
- ↑ "Stepwise oligomerization of murine amylin and assembly of amyloid fibrils". Biophysical Chemistry 180-181: 135–144. 2013. doi:10.1016/j.bpc.2013.07.013. PMID 23974296.
- ↑ "Regulation of the assembly and amyloid aggregation of murine amylin by zinc". Biophysical Chemistry 218: 58–70. November 2016. doi:10.1016/j.bpc.2016.09.008. PMID 27693831.
- ↑ "Amyloidogenesis of the amylin analogue pramlintide". Biophysical Chemistry 219: 1–8. December 2016. doi:10.1016/j.bpc.2016.09.007. PMID 27665170.
External links
- www.symlin.com - product website
- www.amylin.com - Symlin page on the Amylin Pharmaceuticals website
 |
