Lumula (Synonyms: Maxeyprost, Unoprostone Nethyl amide)

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, one would predict very low activity for lumula. The N-ethyl amide prodrug moiety which it inherits from bimatoprost is slow to hydrolyze, and the lower side chain modifications inherited from unoprostone interfere with FP receptor binding. Lumula is therefore a good tool for testing the validity of the alternate mechanism theories.