Pramlintide
2698612
217244636
2008-06-05T05:21:59Z
MAlvis
86878
/* Pharmacology */
{{Drugbox
| IUPAC_name =
| image = Pramlintide sequence.svg
| width = 250
| CAS_number = 151126-32-8
| ATC_prefix =
| ATC_suffix =
| 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 = [[Kidney|Renal]]
| elimination_half-life = Approximately 48 minutes
| excretion =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = C
| pregnancy_category=
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = Rx-only
| legal_status =
| routes_of_administration = [[Subcutaneous injection|Subcutaneous]]
}}
'''Pramlintide acetate''' (Symlin) is a relatively new adjunct treatment for [[Diabetes mellitus|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 [[Blood|bloodstream]] by the [[beta cell|β-cells]] of the [[pancreas]] along with [[insulin]], after a meal.<ref name="pmid17619527">{{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=}}</ref> Like insulin, amylin is deficient in individuals with diabetes.
By augmenting endogenous amylin, pramlintide aids in the absorption of [[glucose]] by slowing [[Stomach|gastric emptying]], promoting [[satiety]] via [[hypothalamus|hypothalamic]] receptors (different receptors than for [[Glucagon-like peptide 1|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.<ref name="pmid16330288">{{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}}</ref> 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 [[amyloid]]ogenic 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:
<code>
Pramlintide: KCNTATCATNRLANFLVHSSNNFGPILPPTNVGSNTY-(NH<sub>2</sub>)<br>
Amylin: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-(NH<sub>2</sub>)<br>
Rat amylin: KCNTATCATQRLANFLVRSSNNFGPVLPPTNVGSNTY-(NH<sub>2</sub>)<br>
</code>
Pramlintide (positively charged) is delivered as an acetate salt.
==References==
<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</br>
{{Pharma-stub}}
{{Oral hypoglycemics and insulin analogs}}
[[Category:Anti-diabetic drugs]]
[[pl:Pramlintyd]]