title: Ammonium chloride and methylamine hydrochloride antagonize clostridial neurotoxins.
abstract: Ammonium chloride (1-8 mM) and methylamine hydrochloride (1-16 mM) produce concentration-dependent antagonism of the onset of neuromuscular blockade caused by botulinum toxin types A, B and C (all at 1 X 10(-11) M) and by tetanus toxin (3 X 10(-10) M). Neither drug antagonizes the onset of paralysis caused by beta-bungarotoxin (1 X 10(-7) M) or by taipoxin (1 X 10(-8) M). At concentrations that produce antagonism of clostridial neurotoxins, ammonium chloride and methylamine hydrochloride (8-10 mM) do not inactivate toxin molecules, nor do they produce irreversible changes in tissue function. When studied under conditions that impose partial synchrony on the mechanism of clostridial neurotoxin action, ammonium chloride and methylamine hydrochloride do not inhibit ligand binding and do not reverse neuromuscular blockade. The drugs act solely to antagonize internalization of toxins by cholinergic nerve endings. As a result of inhibiting the process of internalization, the drugs trap the toxins at an antitoxin sensitive site.
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D000936:Antigen-Antibody Complex; D001904:Botulinum Antitoxin; D004336:Drug Antagonism; D007106:Immune Sera; D007700:Kinetics; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins; D010791:Phrenic Nerve / Q000187:drug effects; D013744:Tetanus Toxin / Q000037:antagonists & inhibitors*
chemical_list: D000936:Antigen-Antibody Complex; D001904:Botulinum Antitoxin; D007106:Immune Sera; D008744:Methylamines; D009498:Neurotoxins; D013744:Tetanus Toxin; D000643:Ammonium Chloride; C027451:methylamine