Disease relevance of TL 1428

• This finding would indicate that the hemicholinium-like toxicity of acetylcholine mustard in the mouse is due to the formation of choline mustard aziridinium ion [1].

High impact information on TL 1428

• The irreversible binding of acetylcholine mustard to muscarinic receptors in intestinal smooth muscle of the guinea-pig [2].
• 2. A value for the apparent binding affinity of acetylcholine mustard and a value for the rate constant for the receptor alkylation reaction have been deduced from the rate of onset of the inhibition of [3-H]-PrBCM binding [2].
• Results of these experiments reveal that the substrates have similar affinities for the enzyme, whereas the maximum velocity for the hydrolysis of acetylcholine mustard was significantly lower than for acetylcholine [3].
• This hemicholinium-like hypothesis for the mechanism of action of choline mustard aziridinium ion is compatible with reported date for toxicity of acetylcholine mustard aziridinium ion in the mouse [4].
• Although difficult to prove with the rat diaphragm it is possible that acetylcholinesterase of this preparation could hydrolyze acetylcholine mustard aziridinium ion at the neurotransmitter site and the resultant choline mustard aziridinium ion would interfere with the uptake of choline and eventually prevent neuromuscular transmission [4].

Biological context of TL 1428

• Evidence was obtained that the acetylcholine mustard aziridinium ion impaired neuromuscular activity when the phrenic nerve was stimulated and that the ion did not directly inhibit muscle contraction [4].

Anatomical context of TL 1428

• Acetylcholine mustard aziridinium ion inhibited the transport of [3H]choline into human erythrocytes [1].

References