Pramlintide

Drugbox
IUPAC_name =

---

width = 250
CAS_number = 151126-32-8
ATC_prefix = A10
ATC_suffix = BX05
ATC_supplemental = [cite web |url=http://www.whocc.no/atcddd/new_atc_ddd.html#ATCDDD_FINAL |title=ATC/DDD Classification (FINAL): New ATC 5th level codes |date=August 27, 2008 |author=WHO International Working Group for Drug Statistics Methodology |publisher=WHO Collaborating Centre for Drug Statistics Methodology |accessdate=2008-09-05]
PubChem = 16132446
DrugBank =
C=171|H=269|N=51|O=53|S=2
molecular_weight = 3951.41 g/mol
bioavailability = 30 to 40%
protein_bound = Approximately 60%
metabolism = Renal
elimination_half-life = Approximately 48 minutes
excretion =
pregnancy_AU =
pregnancy_US = C
pregnancy_category=
legal_AU =
legal_CA =
legal_UK =
legal_US = Rx-only
legal_status =
routes_of_administration = Subcutaneous

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

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.cite journal |author=Jones MC |title=Therapies for diabetes: pramlintide and exenatide |journal=American family physician |volume=75 |issue=12 |pages=1831–5 |year=2007 |pmid=17619527 |doi=] 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.

Approval

Symlin has been approved for use by the FDA by type 1 and type 2 diabetics who use insulin.cite journal |author=Ryan GJ, Jobe LJ, Martin R |title=Pramlintide in the treatment of type 1 and type 2 diabetes mellitus |journal=Clinical therapeutics |volume=27 |issue=10 |pages=1500–12 |year=2005 |pmid=16330288 |doi=10.1016/j.clinthera.2005.10.009] 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

External links

* [http://www.symlin.com www.symlin.com] - product website
* [http://www.amylin.com/pipeline/symlin.cfm www.amylin.com] - Symlin page on the Amylin Pharmaceuticals website