Behavioral and physiological effects of an aziridinium analog of oxotremorine (BM130).

When injected IV BM130, a mustard analog of oxotremorine, acts initially as a cholinergic agonist and thereafter produces a sustained resistance to muscarinic agonists. Control subjects were injected with saline or with BM130A, the active aziridinium intermediate of BM130. Acute injections of BM130 were followed initially by effects that were characteristically cholinomimetic in nature: e.g., tremor, chromodacryorrhea, salivation, hypothermia. The effects were dose-dependent and of limited duration. They were not seen in behavioral variables measured 30 min after drug treatment. Injection of BM130A produced peripheral, but not central effects; saline had no effects. The prediction that initial cholinomimetic effects should be followed by sustained resistance to cholinergic agonists was tested by subjecting animals to oxotremorine challenges at weekly intervals following single injections of BM130. In none of the measures taken did animals injected with BM130A or saline show resistance to the muscarinic challenges. Those administered BM130 showed resistance, which in some variables was sustained for 3-4 weeks. The resistance was statistically significant at high BM130 doses and appeared to be dose dependent over the range studied.