Inhibition of histamine-N-methyltransferase activity by neuromuscular blocking drugs

On the basis of previous findings that histamine-N-methyltransferase (HMT) activity can be significantly enhanced or inhibited by a number of analogues of histamine and drugs containing dialkylaminoalkyl moieties, we investigated whether the neuromuscular blocking drugs alcuronium, d-tubocurarine, decamethonium, succinylcholine, gallamine and pancuronium each of which contain quaternary ammonium groups, influence the activity of HMT. Our findings showed that all six drugs significantly inhibited HMT activity in the concentration range 10(-7)-10(-3) M with alcuronium being the most potent inhibitor (I.D.50 = 2 X 10(-6) M). Activities at these concentrations reveals that alcuronium, pancuronium, d-tubocurarine and gallamine are more potent inhibitors than two of the most potent histamine analogue inhibitors, N tau-methylhistamine and 2-methylhistamine. Alcuronium proved to be of similar potency to the dimaprit analogue, SKF 91488 regarded as one of the most potent HMT inhibitors known. The structurally similar and chemically least complex straight chain neuromuscular blocking compounds, succinylcholine and decamethonium proved to be the least potent inhibitors.