a-Methyl-5HT, AL-34662

t-Butylhydroquinone (t-BHQ), ß-Naphthoflavone, 3-Methylcholanthrene, IL-1a

Travoprost, Latanoprost, Bimatoprost, Unoprostone isopropyl ester a-Methyl-5HT AL-34662

Block P-adrenergic receptors in the ciliary process, decrease AH formation Inhibit ciliary process CA-II and CA-IV to reduce bicarbonate AH production Stimulate (^-adrenergic receptors in the ciliary process and thus decrease AH production. Probably inhibit release of norepinephrine and prevent AH formation; may release natriuretic peptides Inhibition of ciliary process Na+-K+-ATPase leading to direct inhibition of AH formation Prevent ion fluxes of nonpigmented ciliary epithelial cell of the ciliary process to decrease AH formation

Contract ciliary muscle to promote outflow of AH via the TM Inhibition of Na-K-Cl-transporter activity in the TM changes cell shape and volume increases AH efflux Inhibition of rho kinase, myosin-II ATPase, and other kinases modifies actomyosin contractility, leading to changes in the actin cytoskeleton of TM and AH efflux Sequestration of actin monomers and dimers in TM causes cell-shape change and AH efflux Type-A and type-B ANP receptor activation leads to cGMP production, TM relaxation, and AH efflux Release natriuretic peptides increases thus raise cGMP in TM, leading to relaxation and AH efflux Cannabinoid receptor activation opens BKca channels and relaxes TM, promotes AH efflux Probably contraction/relaxation of ciliary muscle and TM (may also promote uveoscleral outflow via release of MMPs) Agents that stimulate local production of MMPs cause ECM degradation around TM and open pathways for AH efflux

Activation of FP receptors in CM and TM releases MMPs that break down ECM around CM and promote AH efflux Contraction/relaxation of CM and TM by activation of 5HT2 receptors may release MMPs and/or PGs or other local mediators that stimulate CM remodeling and thus promote AH efflux or com continued

Table 2 Continued

Class of agent

Specific drug or compound

Mechanism of action

Combination products

Other IOP-lowering agents Melatonin agonists Purines

Phosphatase Inhibitors 5HT1A agonists

Ca2 + -channel blockers a-Adrenoceptor antagonists

Endothelin agonists

Calcitonin gene-related peptide (CGRP)

MMPs and other enzymes or activators of enzymes


Timolol & Latanoprost, Timolol Dorzolamide, Timolol Travoprost

Melatonin and analogs

Agonists and antagonists, diadenosine polyphosphates Calyculin


Verapamil, Nivaldipine, Brovincamine, Nifedipine

Oxymetazoline, Ketanserin

5-Methylurapidil Sarafotoxin-S6c

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