New Approaches to Antiglaucoma Therapy

Sugrue, Michael F.

doi:10.1021/jm9608725

Cited by 86 publications

(52 citation statements)

References 188 publications

(320 reference statements)

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“…Cannabinoids may also inhibit calcium influx through presynaptic ion channels, thereby reducing norepinephrine release in the ciliary body, resulting in decreased aqueous humor production (Sugrue, 1997). In addition, cannabinoids may improve the uveoscleral outflow by dilating blood vessels of the anterior uvea (Porcella et al, 1998), most likely by induction of several outflowfacilitating mediators (Rosch et al, 2006).…”

Section: E Eye Disorders (Glaucoma and Retinopathy)mentioning

confidence: 99%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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Section: E Eye Disorders (Glaucoma and Retinopathy)mentioning

confidence: 99%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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“…36 Topical ␤ -blockers were the fi rst medications that had relatively few visual or ocular side effects, and today they still are widely used anti-glaucoma agents and are considered to be among the fi rst choice of medications for initial therapy in open angle glaucoma. 37 They are effective in IOP-reduction but can produce systemic side effects through direct absorption in the tissues and via the nasolacrimal system.…”

Section: E823mentioning

confidence: 99%

“…59 , 60 Therefore, local activity could be separated from undesired systemic cardiovascular/pulmonary activity, a characteristic much sought after in the search for antiglaucoma therapy. 36 Following unilateral ocular treatment with adaprolol, no effects are produced in the contralateral eye because of systemic inactivation.…”

Section: E827mentioning

confidence: 99%

Ophthalmic drug design based on the metabolic activity of the eye: Soft drugs and chemical delivery systems

Bodor

Buchwald²

2005

AAPS J

104

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A BSTRACTDespite its apparent easy accessibility, the eye is, in fact, well protected against the absorption of foreign materials, including therapeutic agents, by the eyelids, by the tearfl ow, and by the permeability barriers imposed by the cornea on one side and the blood-retinal barrier on the other. Most existing ophthalmic drugs were adapted from other therapeutic applications and were not specifi cally developed for the treatment of eye diseases; hence, they are not well suited to provide eye-specifi c effects without causing systemic side effects. A real breakthrough in the area of ophthalmic therapeutics can be achieved only by specifi cally designing new drugs for ophthalmic applications to incorporate the possibility of eye targeting into their chemical structure. Possibilities provided along these lines by designing chemical delivery systems (CDSs) and soft drugs within the framework of retrometabolic drug design are reviewed here. Both are general concept applicable in almost any therapeutic area. This review will concentrate on ␤ -adrenergic agonists and anti-infl ammatory corticosteroids, where clinical results obtained with new chemical entities, such as betaxoxime, adaprolol, loteprednol etabonate, and etiprednol dicloacetate, exist to support the advantages of such metabolism-focused, ophthalmic-specifi c drug design approaches.K EYWORDS: beta-blockers , corticosteroids , eye-targeted delivery , glaucoma , intraocular pressure , oxime OCULAR DRUG DESIGN AND DELIVERY: CHALLENGESFor the therapeutic treatment of most ocular problems, topical administration clearly seems the preferred route, because for systemically administered drugs, only a very small fraction of their total dose will reach the eye from the general circulatory system. Even for this fraction, distribution to the inside of the eye is further hindered by the blood-retinal barrier (BRB), which is almost as effective as the blood-brain barrier (BBB) in restricting the passage of xenobiotics from the blood stream. 1 At fi rst sight, the eye seems an ideal, easily accessible target organ for topical treatment. However, the eye is, in fact, well protected against absorption of foreign materials, fi rst by the eyelids and tear-fl ow and then by the cornea, which forms the physical-biological barrier. When any foreign material or medication is introduced on the surface of the eye, the tear-fl ow immediately increases and washes it away in a relatively short time. Under normal conditions, the eye can accommodate only a very small volume without overfl owing. Commercial eyedrops have a volume of ~30 L, which is about the volume of the conjunctival sac in humans; however, after a single blink, only an estimated 10 L remains. 2 Consequently, there is a window of only ~5 to 7 minutes for any topically introduced drug to be absorbed, and in many cases, no more than 2% of the medication introduced to the eye will actually be absorbed. 2-4 The rest will be washed away and absorbed through the nasolacrimal duct and the mucosal membranes of the nasa...

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“…41 Green et al 42 showed that D 9 -THC decreased the secretion of ciliary processes and led to a dilatation of the ocular blood vessels through a possible b adrenergic action. In addition, Sugrue 43 indicated that cannabinoids may inhibit calcium influx through presynaptic channels and in this way reduce the noradrenaline release in the ciliary body, leading to a decrease in the production of aqueous humour. Porcella et al 10 proposed that cannabinoids might be acting as vasodilators on blood vessels of the anterior uvea, thus improving the aqueous humour uveoscleral outflow.…”

Section: Mechanism Of Iop Reductionmentioning

confidence: 99%