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Item Omidenepag isopropyl ophthalmic solution for open-angle glaucoma and ocular hypertension: an update(Taylor & Francis, 2021) Aihara, Makoto; Aung, Tin; Bacharach, Jason; Cantor, Louis; Kook, Michael; Nakazawa, Toru; Park, Ki Ho; Lu, Da-Wen; Ophthalmology, School of MedicineIntroduction: Current medical therapy for glaucoma consists of topical agents that lower intraocular pressure (IOP). Prostaglandin F2α analogues, the most commonly used class of IOP-lowering drugs, bind to prostaglandin FP receptors in tissues of the uveoscleral pathway. This binding increases the expression of matrix metalloproteinases, which degrade the extracellular matrix of the ciliary body, creating inter-muscular spaces allowing aqueous humor to exit the eye. Drawbacks to prostaglandin F2α analogues include cosmetic side effects, especially prostaglandin-associated periorbitopathy (PAP) syndrome. Areas covered: This review describes the novel prostaglandin E2 receptor antagonist, omidenepag isopropyl, which reduces IOP by improving drainage of uveoscleral and trabecular outflow, increasing the facility of outflow. In contrast to prostaglandin F2α analogues, omidenepag does not inhibit adipogenesis or promote eyelash growth. This review describes preclinical studies of omidenepag, published results of phase I–III clinical trials, and preliminary results of phase III trials currently in progress. Expert opinion: Omidenepag appears to provide IOP reductions comparable to those of prostaglandin F2α analogues, but without the cosmetic side effects common to prostaglandin F2α analogues, especially PAP syndrome. The lack of association between omidenepag and PAP suggests that long-term use of this agent may have advantages in patients with glaucoma.Item Prostaglandin-Mediated Reinstatement of Drug Taking After Alcohol Drinking by Female Adolescent Rats(2022-04) Kline, Hannah L.; Engleman, Eric A.; Atwood, Brady K.; McKinzie, David L.; Truitt, William A.; Yamamoto, Bryan K.Adolescent alcohol abuse is a global problem that initiates lifelong addiction. Alcohol use during adolescence is associated with subsequent Meth dependence in humans. Specifically, female adolescents are particularly vulnerable to serial alcohol and Meth use. However, it is unknown if prior voluntary alcohol drinking impacts subsequent Meth-taking in female adolescent rats. Both alcohol and Meth increase the prostaglandin synthesis enzyme cyclooxygenase-2 (COX-2) in the brain but the effect of serial exposure to alcohol and Meth on COX-2 has not been determined. The first study uses a novel method of serial voluntary alcohol drinking and Meth self-administration in female adolescent rats to model human patterns of co-abuse. Prior alcohol drinking did not affect subsequent Meth self-administration, but it reduced the cue-primed reinstatement of Methseeking after abstinence from Meth. Rats with a history of adolescent alcohol drinking also had increased COX-2 in the dorsal striatum, regardless of subsequent Meth selfadministration. These findings demonstrate that a history of adolescent alcohol drinking does not alter Meth self-administration but persistently reduces cue-primed Meth seeking and increases COX-2 after prolonged abstinence from alcohol. To further examine the role of COX-2 in alcohol drinking, the second study found that adolescent alcohol drinking not only increased COX-2 after four weeks of alcohol abstinence, but also increased endothelin-1 (ET-1) and prostaglandin E2 (PGE2) in the dorsal striatum. Furthermore, adolescent alcohol drinking increased alcohol drinking after abstinence, and this increase was attenuated by treatment with the COX-2 inhibitor nimesulide during abstinence. Antagonism of the interaction between PGE2 and its receptor 1 (EP1) also attenuated the increase in relapse drinking and restored alcohol drinking to the rate of alcohol naïve rats. Overall, these experiments identified a prostaglandin-mediated mechanism that is a putative target for the treatment of alcohol relapse following abstinence in individuals with a history of adolescent alcohol abuse.