anandamide and Glaucoma

Glaucoma is a slowly progressive optic neuropathy that is one of the leading causes of legal blindness throughout the world. Currently there is a limited group of topical drugs for the medical treatment of glaucoma is currently limited, and research needs to be focused on new therapeutic horizons, such as the potential usefulness of the cannabinoid agonists for the treatment of glaucoma.. To review the current scientific literature related to the beneficial effects derived from the different ways of administration of cannabinoids indicated for the glaucomatous optic neuropathy.. Cannabinoid receptors have shown an intense expression in ocular tissues implicated in the regulation of the intraocular pressure, as well as inner layers of the retina. Through activation of CB1 and CB1 specific receptors and through other still unknown pathways, the cannabinoid agonists have shown both a clear hypotensive, as well as an experimentally proved neuroprotective effect on retinal ganglion cells.. Some cannabinoid agonists (WIN 55212-2, anandamide) have demonstrated, in experimental studies, to act as «ideal drugs» in the management of glaucoma, as they have been shown to have good tolerability after topical application, efficiently reduce intraocular pressure, and behave as neuroprotectors on retinal ganglion cells. Further studies as regards the safety and clinical assays must be carried out in order to examine the effectiveness of these drugs for the treatment of glaucoma in our daily clinical practice.

Topics: Animals; Arachidonic Acids; Benzoxazines; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Cannabinoids; Drug Administration Routes; Drug Evaluation, Preclinical; Endocannabinoids; Excitatory Amino Acid Antagonists; Eye Proteins; Glaucoma; Glutamic Acid; Humans; Intraocular Pressure; Mammals; Morpholines; Naphthalenes; Neuroprotective Agents; Optic Nerve; Polyunsaturated Alkamides; Receptors, Cannabinoid; Retinal Ganglion Cells; Vasodilator Agents

The discovery of anandamide and 2-arachidonyl glycerol (2-AG) as naturally occurring mammalian endocannabinoids has had important and wide-reaching therapeutic implications. This, to a large extent, ensues from the complexity of endocannabinoid biology. One facet of endocannabinoid biology now receiving increased attention is the cyclo-oxygenase-2 (COX-2) derived oxidation products. Anandamide and 2-AG are oxidized to a range of PG-ethanolamides and PG-glyceryl esters that closely approaches that of the prostaglandins (PGs) formed from arachidonic acid. The pharmacology of these electrochemically neutral PG-ethanolamides (prostamides) and PG-glyceryl esters appears to be unique. No meaningful interaction with natural or recombinant prostanoid receptors is apparent. Nevertheless, in certain cells and tissues, prostamides and PG-glyceryl esters exert potent effects. The recent discovery of selective antagonists for the putative prostamide receptor has been a major advance in further establishing prostamide pharmacology as an entity distinct from prostanoid receptors. Since discovery of the prototype prostamide antagonist (AGN 204396), rapid progress has been made. The latest prostamide antagonists (AGN 211334-6) are 100 times more potent than the prototype and are, therefore, sufficiently active to be used in living animal studies. These compounds will allow a full evaluation of the role of prostamides in health and disease. To date, the only therapeutic application for prostamides is in glaucoma. The prostamide analog, bimatoprost, being the most effective ocular hypotensive drug currently available. Interestingly, PGE(2)-glyceryl ester and its chemically stable analog PGE(2)-serinolamide also lower intraocular pressure in dogs. Nevertheless, the therapeutic future of PGE(2)-glyceryl ester is more likely to reside in inflammation.

Topics: Animals; Arachidonic Acids; Cannabinoid Receptor Modulators; Cyclooxygenase 2; Endocannabinoids; Glaucoma; Humans; Polyunsaturated Alkamides; Prostaglandin Antagonists

The active principle in marijuana, Delta(9)-tetrahydrocannabinol (THC), has been shown to have wide therapeutic application for a number of important medical conditions, including pain, anxiety, glaucoma, nausea, emesis, muscle spasms, and wasting diseases. Delta(9)-THC binds to and activates two known cannabinoid receptors found in mammalian tissue, CB1 and CB2. The development of cannabinoid-based therapeutics has focused predominantly on the CB1 receptor, based on its predominant and abundant localization in the CNS. Like most of the known cannabinoid agonists, Delta(9)-THC is lipophilic and relatively nonselective for both receptor subtypes. Clinical studies show that nonselective cannabinoid agonists are relatively safe and provide therapeutic efficacy, but that they also induce psychotropic side effects. Recent studies of the biosynthesis, release, transport, and disposition of anandamide are beginning to provide an understanding of the role of lipid transmitters in the CNS. This review attempts to link current understanding of the basic biology of the endocannabinoid nervous system to novel opportunities for therapeutic intervention. This new knowledge may facilitate the development of cannabinoid receptor-targeted therapeutics with improved safety and efficacy profiles.

Topics: Amidohydrolases; Analgesics; Animals; Anti-Anxiety Agents; Antiemetics; Appetite Stimulants; Arachidonic Acids; Brain Chemistry; Cannabinoid Receptor Modulators; Cannabinoids; Endocannabinoids; Glaucoma; Humans; Movement Disorders; Neuroprotective Agents; Polyunsaturated Alkamides; Receptors, Cannabinoid; Receptors, Drug; Signal Transduction

Cannabinoid CB(1) receptors are involved in ocular physiology and may regulate intraocular pressure (IOP). However, endocannabinoid levels in human ocular tissues of cornea, iris, ciliary body, retina, and choroid from normal and glaucomatous donors have not been investigated. Anandamide (N-arachidonoylethanolamine; AEA), 2-arachidonoylglycerol (2-AG), and the anandamide congener, palmitoylethanolamide (PEA), were detected in all the human tissues examined. In eyes from patients with glaucoma, significantly decreased 2-AG and PEA levels were detected in the ciliary body, an important tissue in the regulation of IOP. The findings suggest that these endogenous compounds may have a role in this disease, particularly with respect to regulation of IOP.

Topics: Aged; Amides; Arachidonic Acids; Cannabinoid Receptor Modulators; Ciliary Body; Endocannabinoids; Ethanolamines; Eye; Glaucoma; Glycerides; Humans; Middle Aged; Organ Specificity; Palmitic Acids; Polyunsaturated Alkamides