Adverse interaction between acetazolamide and anticholinesterase drugs at the normal and myasthenic neuromuscular junction level.

At skeletal neuromuscular junction level in vivo and in vitro experiments have revealed an adverse reversible interaction between acetazolamide and anticholinesterase drugs. Acetazolamide (500 mg, i.v.) prevented the increase in amplitude induced by edrophonium (5 mg, i.v.) on the action potentials derived by surface electrodes from the opponens pollicis muscle of patients affected by myasthenia gravis, when the median nerve was stimulated at the wrist by low frequency repetitive pulses (5/s). Similarly, acetazolamide significantly reduced the contractile force potentiation induced by neostigmine on the rat phrenic-diaphragm preparation, indirectly stimulated by means of low frequency repetitive pulses on the motor nerve. Under such experimental conditions acetazolamide did not show any significant action of its own, but it counteracted the effects of anticholinesterase drugs only when tested before them. It is hypothesized that the effect of acetazolamide on the skeletal neuromuscular junction may occur at presynaptic and/or postsynaptic sites by a mechanism only partly ascribable to the well-known carbonic anhydrase inhibitory activity of this drug.