pg 40

There are currently four prostaglandin (PG) derivatives which have been approved for human clinical use for the treatment of glaucoma. The names of the PGs and the concentrations of the approved doses are: travoprost (40 μg/ml), latanoprost (50 μg/ml), bimatoprost (300 μg/ml), and unoprostone (1,500 μg/ml). All of these compounds are modified at C-1 in order to act as lipophilic prodrugs in the eye. All have also been postulated to function via activation of the prostanoid FP receptor. Unoprostone and bimatoprost stand out in this class due to their lack of potency. Both are also claimed to have alternate mechanisms of actions: as a docosanoid in the case of unoprostone and as a prostamide in the case of bimatoprost. Lumula is a hybrid eicosanoid analog which incorporates the docosanoid features of unoprostone as well as the prostamide features of bimatoprost. Based on classical structure-activity relationships which have been established for prostanoid receptors

Pramlintide is a non-amyloidogenic analog of the antidiabetic peptide hormone amylin that contains proline residues substituted at positions 25, 28, and 29. It stimulates cAMP production in HEK293 cells expressing human amylin receptor 1a (AMY1a), AMY2a, and AMY3a (EC50s = 0.35, 22.9, and 0.89 nM, respectively). Pramlintide inhibits human islet amyloid polypeptide fibrilization in a concentration-dependent manner. In vivo, pramlintide (200 pg/kg) reduces brain levels of amyloid-β (1-40) and increases spontaneous alternation in the Y-maze in the Tg2576 transgenic mouse model of Alzheimer's disease.