Uptake of ¹⁴C‐Neostigmine in Rat Striated Muscles

Abstract

The uptake of leC-neostigmine in striated muscles was studied after intravenous injection into rats and in the isolated rat diaphragm. 120 minutes after the intravenous injection of W-neostigmine (100 pg/kg) the 14C-concentration in the quadriceps, sternomastoid and intercostal muscles was 3/3-W of the concentration in the plasma, whereas the 14Gconcentration in the diaphragm was about double the concentration in the plasma. After continuous intravenous infusion of 14C-neostigmine the distribution pattern was the same as after a single injection. Paper chromatography showed that the radioactivity in the diaphragm was due partly to unchanged neostigmine, partly to a metabolite. In the isolated diaphragm unchanced 14C-neostigmine accumulates against an apparant concentration gradient. The uptake is partly saturable and energy-dependent. It is suggested that intracellular accumulation of neostigmine andlor its metabolites may be causally related to the respiratory failure following overdosage of neostigmine.

Studies on the Uptake of 14C‐Neostigmine in the Isolated Rat Diaphragm

“…Studies in our laboratory on the uptake of 14C-neostigmine in different groups of rat striated muscles have demonstrated that the uptake of radioactivity in vivo in the muscles is higher than would be expected in the case of a distribution limited to the extracellular phase of the muscles. The diaphragm was remarkable by having a much higher uptake than the rest of the muscles (BROEN CHRISTENSEN & HELLEBERG 1974). Neostigmine not only inhibits the acetylcholinesterase but also has a direct action on the skeletal muscle and is capable of producing neuromuscular block (RIKER & WESCOE 1946).…”

Studies on the Uptake of 14C‐Neostigmine in Rat Diaphragm: Effects of Chronic Treatment with Anticholinesterases and Chronic Denervation

“…Previous studies in our laboratory on the distribution of W-neostigmine after single intravenous injection into rats have demonstrated that the compound and its metabolites accumulate in the diaphragm. It was suggested that this accumulation might be causally related to the respiratory failure sometimes seen in myasthenic patients treated with large doses of neostigmine (BROEN CHRISTENSEN & HELLEBERG 1974).…”