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Pramlintide



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.

Additional recommended knowledge

Contents

Pharmacology

It is derived from amylin, a hormone that is released into the bloodstream, in a similar pattern as insulin, after a meal.[1] Like insulin, amylin is deficient in individuals with diabetes.

By substituting for amylin, pramlintide aids in the absorption of glucose by slowing gastric emptying, promoting satiety, and inhibiting inappropriate secretion of glucagon, a catabolic hormone that opposes the effects of insulin and amylin.

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.

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.

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.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Pramlintide". A list of authors is available in Wikipedia.
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