PT-141 / Tadalafil / Oxytocin – Gel Troche

PT-141^1,2

Bremelanotide (PT-141), a MCR agonist, non-selectively works on several receptor subtypes MC1R-MC5R in the central nervous system. MC1R and MC4R are thought to be the most relevant. MC4R are commonly present in the central nervous system. Although the mechanism of action is not fully elucidated, the drug is thought to activate pathways in the brain that are involved in sexual responses.

Tadalafil^3-5

Phosphodiesterase (PDE) has many isoforms and is an enzyme that has many functions in the body including degrading the effect of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE5 is an enzyme that is found in many parts of the body including in the smooth muscle of the corpus cavernosum, prostate, bladder, the vascular and visceral smooth muscle, skeletal muscle, urethra, platelets, kidney, lung, cerebellum, heart, liver, testis, seminal vesicle, and pancreas. Tadalafil is a selective inhibitor of PDE5, the enzyme responsible for the degradation of cGMP. The drug has selective activity on PDE5 than other phosphodiesterase isoforms. Tadalafil activity on PDE5 is more than 10,000-fold more than for PDE1, PDE2, PDE4, and PDE7 enzymes. Increased cGMP leads to smooth muscle relaxation in the corpus cavernosum which can help in maintaining an erection.

Oxytocin^6-11

Oxytocin causes G-protein coupled receptors to increase intracellular calcium which leads to uterine contraction. The stimulation of uterine contractions causes more oxytocin to be released. As more oxytocin is released it positively influences even more release of oxytocin. This release of oxytocin is called positive feedback which is much different than how many hormones work in the endocrine system. Oxytocin administered exogenously causes the same response as endogenously produced oxytocin. Not only does oxytocin stimulate uterine contractions, but it also causes contractions of myoepithelial cells in the alveolar ducts found in female breast tissue. These contractions force milk from these ducts into even larger sinuses, which subsequently enables milk expulsion. When a baby attempts to latch onto the mother’s breast it causes oxytocin secretion into the blood in the same manner as vaginal delivery; instead of uterine contractions, milk is ejected from the breast. Similar to the actions of oxytocin in the uterus to stimulate contractions during delivery, milk-ejection from breast tissue occurs due to positive feedback. In the brain, it is proposed that oxytocin stimulates social and sexual function by its activity in many areas of the brain including its activity on neurotransmitters.