Moxaverine (hydrochloride)

Moxaverine hydrochloride is a phosphodiesterase (PDE) inhibitor. Moxaverine hydrochloride also interacts with calmodulin (calmodulin), thereby enhancing the inhibition of calmodulin-dependent PDE. Moxaverine hydrochloride can be used in studies related to microcirculation regulation and ocular tissue distribution^{[1][2][3][4][5][6]}. In Vitro:Moxaverine hydrochloride (10⁻⁵-10⁻² M; in hypertonic conditions of 400 mosmol/L and lactic acidosis at pH 6.8) restores the normal discoid morphology of stressed red blood cells and improves their microrheological filtration performance under low shear stress conditions^[1].
¹⁴C-labeled moxaverine hydrochloride (33 μM; up to 4 h) exhibits high bidirectional permeability in HCE-T, C-HCE, ex vivo human cornea and ex vivo rabbit cornea models, with P_app values of 13.42/17.49, 5.84/6.82, 5.42/3.76 and 5.16/2.39 × 10⁻⁶ cm/s for the apical-to-basolateral/basolateral-to-apical directions, respectively^[3].
¹⁴C-labeled moxaverine hydrochloride efficiently permeates through primary rabbit corneal epithelial cell layers. It shows no significant transport directionality in the presence or absence of benzalkonium chloride and EDTA, indicating that its corneal absorption mainly occurs via transcellular passive diffusion^[5]. In Vivo:Moxaverine hydrochloride (1.28 × 10⁻³ M; 50 μL/eye; topical ocular administration; ¹⁴C tracing; 30 and 120 min) distributes mainly in the conjunctiva, cornea and iris/ciliary body, and can penetrate into the retina in male Dutch-belted pigmented rabbits. Compared with intravenous administration, the plasma level after topical ocular administration is significantly lower, and the content in the retina continues to increase at 120 min^[5].
After intravenous administration to male Dutch-belted pigmented rabbits, moxaverine hydrochloride (1.28 × 10⁻³ M; i.v.; ¹⁴C tracing; 30 and 120 min) can penetrate into the retina, but its retinal content decreases at 120 min compared with that at 30 min; its scleral contents at both 30 and 120 min are lower than those after topical ocular administration^[5].
Moxaverine hydrochloride (50 μL/eye; topical ocular administration; ¹⁴C-moxaverine-HCl tracing; 30 and 120 min) distributes mainly in the conjunctiva, cornea and iris/ciliary body in male Dutch-belted pigmented rabbits, with no measurable levels detected in the lens; the concentration in the retina is comparable to that after intravenous administration at 30 min, and higher than that after intravenous administration at 120 min, while the plasma level after topical ocular administration is lower than that after intravenous administration^[2].