Anti-cholinesterase activity of 1-α-acetylmethadol: Relationship to bradycardia

1. 1. 1-α-Acetylmethadol (LAAM) and its major metabolites, 1-α-acetylnormethadol (N-LAAM) and 1-α-acetyldinormethadol (DN-LAAM), were shown to exert significant anticholinesterase activity in preparations of guinea pig heart homogenate, guinea pig plasma, purified acetylcholinesterase (EC 3.1.1.7) and purified butyrylcholinesterase (EC 3.1.1.8), P 2. 2. LAAM and congeners did not decrease heart homogenate cholinesterase activity at low concentrations (5 × 10−6M) which produce bradycardia in vitro that can be blocked completely with atropine. 3. 3. The data suggest that cholinesterase inhibition does not contribute to the bradycardia effected by lower concentrations of LAAM. However, cholinesterase inhibition may contribute to LAAM-induced bradycardia at higher concentrations.