Br J Pharmacol Chemother. 1964 Aug;23(1):131-50. doi: 10.1111/j.1476-5381.1964.tb01574.x.


A survey has been made of the effects on junctional transmission of the complete series of polymethylene bis-trimethylammonium (BTM) and bis-triethylammonium (BTE) salts from the decamethylene compounds (BTM 10 and BTE 10) to those with twenty-one methylene groups in the chain. These were tested for their ability to cause contracture of the isolated chick biventer cervicis preparation, and for their ability to block the twitch responses of this preparation, those of the rat isolated diaphragm preparation, and those of the cat tibialis anterior preparation. They were also tested for their ability to block transmission in the cat superior cervical ganglion, to block the actions of acetylcholine on the guinea-pig isolated ileum, and for ability to inhibit the hydrolysis of acetylcholine by acetylcholinesterase. Their electrical conductivity has been measured in aqueous solution. Ability to cause contracture of the chick biventer cervicis is confined to the compounds BTM 10 to 15; BTE 10, 11 and 12 have some weak activity but the other BTE compounds, and the BTM compounds with more than fifteen methylene groups, have virtually no activity. In the BTE series both neuromuscular blocking and ganglion-blocking activities increase with chain length up to a maximum in the region of BTE 15 to 17 and then decline. In the BTM series ganglion-blocking activity increases with chain length in much the same way as in the BTE series, though the maximum activity is at a slightly longer chain length. At the neuromuscular junction an increase in chain length beyond BTM 10 leads to a decline in activity but this returns to some extent at longer chain lengths, reaching a second maximum at BTM 18, above which it declines further. At the ganglion BTE 16 is only slightly more active than BTM 16 and about five-times as active as hexamethonium; at the neuromuscular junction in the cat BTE 16 is about five-times as active as BTM 16 and about eight-times as active as (+)-tubocurarine. The affinity of the BTE compounds for the postganglionic acetylcholine receptors of the guinea-pig ileum reaches a maximum at BTE 14 but does not decline significantly with further increase in chain length. Anticholinesterase activity, likewise, does not alter significantly between BTM 12 and BTM 21 and the activity of the compounds in the BTE series appears to be similar. This property could conceivably be modifying the actions of some of the intermediate compounds but is not likely to be affecting those of the more active ones. The conductivity experiments indicate that micelle formation could be limiting the actions of the compounds with 20 or 21 methylene groups, but is not likely to be affecting those of the other compounds. The results suggest that there is a regular increase with chain length of the affinity of these compounds for the receptors in the ganglia and at the neuromuscular junction but that efficacy in causing contracture is limited to compounds with three methyl groups in the cationic head and a chain of about ten methylene groups. The connexion between this ability to depolarize and the ability to block transmission by desensitization is discussed.

MeSH terms

  • Acetylcholine*
  • Acetylcholinesterase*
  • Ammonium Compounds*
  • Animals
  • Bis-Trimethylammonium Compounds*
  • Cats
  • Cholinesterase Inhibitors*
  • Diaphragm*
  • Ganglia*
  • Ganglionic Blockers*
  • Guinea Pigs
  • Hexamethonium Compounds*
  • Ileum*
  • Neural Conduction*
  • Neuromuscular Junction*
  • Pharmacology*
  • Poultry*
  • Quaternary Ammonium Compounds*
  • Rats
  • Research*
  • Salts*
  • Sensory Receptor Cells*
  • Tubocurarine*


  • Ammonium Compounds
  • Bis-Trimethylammonium Compounds
  • Cholinesterase Inhibitors
  • Ganglionic Blockers
  • Hexamethonium Compounds
  • Quaternary Ammonium Compounds
  • Salts
  • Acetylcholinesterase
  • Acetylcholine
  • Tubocurarine