Biomaterial Database

Inhibition of histamine-N-methyltransferase activity by neuromuscular blocking drugs. 1985

D G Harle, and B A Baldo, and M M Fisher

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.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008780	Methyltransferases	A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.	Methyltransferase
D009466	Neuromuscular Blocking Agents	Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc.	Neuromuscular Blocker,Neuromuscular Blocking Agent,Neuromuscular Blockers,Agent, Neuromuscular Blocking,Agents, Neuromuscular Blocking,Blocker, Neuromuscular,Blockers, Neuromuscular,Blocking Agent, Neuromuscular,Blocking Agents, Neuromuscular
D010197	Pancuronium	A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than CURARE but has less effect on the circulatory system and on histamine release.	Pancuronium Bromide,Pancuronium Curamed,Pancuronium Organon,Pavulon,Bromide, Pancuronium
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003650	Decamethonium Compounds	Compounds that contain the decamethylenebis(trimethyl)ammonium radical. These compounds frequently act as neuromuscular depolarizing agents.	Compounds, Decamethonium
D005703	Gallamine Triethiodide	A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)	Gallamine,Gallamonium Iodide,Flaxedil,Gallamine Triethochloride,Gallamine Triethyl Iodide,Iodide, Gallamine Triethyl,Iodide, Gallamonium,Triethiodide, Gallamine,Triethochloride, Gallamine,Triethyl Iodide, Gallamine
D006637	Histamine N-Methyltransferase	An enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to histamine, forming N-methylhistamine, the major metabolite of histamine in man. EC 2.1.1.8.	Histamine Methyltransferase,Histamine N Methyltransferase,Methyltransferase, Histamine,N-Methyltransferase, Histamine
D000443	Alcuronium	A non-depolarizing skeletal muscle relaxant similar to TUBOCURARINE. It is used as an anesthesia adjuvant.	Alcuronium Chloride,Allnortoxiferine,Diallylnortoxiferine,Alcuronium Dichloride,Alloferin,Dialferine,N,N'-Diallylnortoxiferinium Dichloride,Dichloride, Alcuronium,Dichloride, N,N'-Diallylnortoxiferinium
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia