ABSTRACT
Although bimatoprost shows some structural similarities with PGF2a (Figure 6.2), it was reported not to bind to the FP receptor and its mode of action is not fully understood.7 It is chemically related to prostamide F, a naturally occurring substance which is derived from the endogenous cannabinoid receptor agonist anandamide (arachidonylethanolamide, AEA; see Figure 6.3) by the contribution of cyclooxygenase-2. The prostamide F receptor has not yet been identified. However, recent reports show that bimatoprost and its free acid replaced [3H]-PGF2a from the FP receptor and mobilized intracellular calcium via cloned human FP receptors expressed in human embryonic kidney cells.8 This effect could be blocked by an FP receptor antagonist. In the same line of evidence, further studies of bimatoprost metabolism in corneal tissue showed that bimatoprost is converted in vitro to 17-phenyl-18,19,20-trinor prostaglandin F2a, which is identical to the free acid of latanoprost with the exception of a double, rather than a single bond at the 13-14 position.9 If this occurs in vivo as well this finding may explain the IOP-reducing effect of bimatoprost. The onset of the IOP-reducing effect is about 3 to 4 hours after administration for all of these analogs; the maximum effect, achieved after 8 to 12 hours, is maintained over 24 hours.
