Effects of thymoxamine on corneal endothelium.

We have investigated the effects of 0.02 and 0.2% thymoxamine hydrochloride on the isolated rabbit corneal endothelium. The corneal swelling rate, measured by specular microscopy, indicated that 0.02% thymoxamine caused a swelling rate equal to controls while a 0.2% concentration caused a significantly increased swelling rate (34.1 vs 10.3 microns/h; P less than 0.05). The data suggests that the maximum recommended intracameral concentration of thymoxamine be 0.02% in order to allow a 10-fold safety factor for the corneal endothelium.

Toxicity of intracameral thymoxamine.

The anterior chamber of adult pigmented rabbits was perfused with 1 ml of either 0.02% or 0.2% thymoxamine hydrochloride in Balanced Salt Solution. Contralateral eyes were either perfused with BSS alone or remained untouched. Measurements were made of corneal thickness and intraocular pressure prior to perfusion and at days 1, 2, 3 and 7 after perfusion. Observations were made of toxic reactions of ocular tissues using slit-lamp biomicroscopy. No effects were noted with 0.02% thymoxamine but 0.2% caused corneal swelling and a reduction in intraocular pressure at day 1. Neither concentration caused any observable toxic responses. Morphologic studies confirm the absence of effects by 0.02% thymoxamine, and that 0.2% causes disturbance of both corneal endothelium and iris-ciliary processes. This data, together with an earlier report on in vitro studies of thymoxamine, allows the conclusion that 0.02% thymoxamine is a safe concentration for use in the anterior chamber and 0.2% yields adverse reactions.

Morphologic and physiologic effects of thymoxamine on corneal endothelium and ciliary processes.

Either 0.2 or 0.02% thymoxamine hydrochloride was perfused across the endothelium of isolated rabbit corneas in a specular microscope. Treated corneas did not swell, compared to controls, when perfused with 0.02% thymoxamine, but swelled at 34 microns/hr after 0.2% thymoxamine compared to 10 microns/hr of controls. Morphologically, 0.2% thymoxamine caused many intracellular vacuoles, with far fewer changes after 0.02%. Replacement of the aqueous humor with 0.02% thymoxamine caused no effect on either the corneal endothelium or ciliary process, whereas 0.2% caused small, but significant, changes in both tissues.

Safety of intracavernous injections using an alpha-blocking agent.

We tested the possibility of using intracavernous injections of the alpha-blocking agent moxisylyte (6-acetoxy-thymoxy-ethyl-dimethylamine) as treatment of erectile impotence. Laboratory studies proved moxisylyte to be more active than saline (double-blind with crossover) but less active than papaverine (crossover), since it induced prolonged erection in most patients but rigid erection in only a few. However, penile vibration proved to enhance the moxisylyte effects, the combination resulting in rigid erection in 5 of 8 patients tested. Repeated office injections of moxisylyte in 70 patients resulted in clear improvement of impotence during the subsequent weeks in 50 per cent of the psychogenic, and 18 per cent of the organic and mixed impotent patients. Of 91 impotent patients 42 achieved satisfactory intercourse within 2 hours after an office injection, although previously the same dose induced a rigid erection in the office in only 24. Of 37 patients instructed in moxisylyte self-injections 92 per cent achieved successful results without any significant side effect. The main advantage of moxisylyte proved to be its safety, allowing for less compelling precautions than with papaverine: only 2 of the 170 patients injected with moxisylyte at our clinic had prolonged erections, that is 1.1 per cent compared to 14 per cent in a personal series who received papaverine. In regard to the therapeutic applications of intracavernous injection facilitating drugs, such as moxisylyte, should be tried first, with use of the more potent but also more dangerous drugs, such as papaverine, only when impotence fails to improve.

In vitro and in vivo alpha-blocking activity of thymoxamine and its two metabolites.

The alpha-adrenoceptor potency of thymoxamine and its two metabolites deacetylthymoxamine and demethyldeacetylthymoxamine were determined on the contraction of rat vas deferens induced by noradrenaline, the blood pressure increase induced by noradrenaline given i.v. to dogs and the contraction of the nictitating membrane induced by electrical stimulation in cats. In vivo the three drugs were administered at 6.35 x 10(-6) mol kg-1 intravenously. Deacetylthymoxamine presented nearly the same alpha-blocking activity as the parent drug. This was ascribed in vivo to the rapid deacetylation of thymoxamine. Demethyldeacetylthymoxamine was less active. In vitro its pA2 was 6.20 +/- 0.09 compared with 6.75 +/- 0.20 for thymoxamine and 6.57 +/- 0.13 for deacetylthymoxamine. In vivo, it was inactive in dog and less active than the other two drugs soon after its administration in the cat. The oral LD 50 values in the mouse for the three drugs were respectively 0.81, 0.71 and 1.14 mmol kg-1 for thymoxamine, deacetylthymoxamine and demethyldeacetylthymoxamine.