Siponimod and Cognition in Secondary Progressive Multiple Sclerosis

Uptake of a neuromuscular blocking agent labeled with I¹³¹ has been recorded in various muscles and in tendon. The compound used, iodocholinium, was an iodo-ethyl derivative of decamethonium (C-10). In skeletal muscle, the uptake was comparatively high in the 12-hour period during which block was increasing, while in smooth muscle and tendon, uptakes were much lower. Inorganic iodine as NaI¹³¹ was concentrated by skeletal muscle to a very low extent compared with that of the organically-bound I¹³¹ in all other tissues studied. d-Tubocurarine (DTC) markedly inhibited the uptake of iodocholinium in skeletal muscle, although there was no detectable effect on smooth muscle and tendon. Outward movement of labeled iodocholinium has also been studied in isolated guinea-pig diaphragm and rabbit lumbrical muscle and has been shown to occur in two phases. There is an initial, rapid outward movement, virtually complete in 20 minutes, of an amount of drug which corresponds to that contained in the interfiber spaces (0.30 by volume of the muscle). The half time for this process is about 2½ minutes. The apparent diffusion coefficient of labeled iodocholinium through the interspaces has been estimated to be 2.5 x 10^-6 cm² sec^-1. The remainder of the drug is lost at a much slower rate and appears to be coming from inside the muscle fibers, and though variable has a half-time of about 4 to 6 hours. Curare added to the preparation during release of iodocholinium has no detectable effect, in contrast to its effects on iodocholinium uptake.