The neuromuscular and autonomic blocking effects of azasteroids containing choline or acetylcholine fragments

I. G. MARSHALL, A. L. HARVEY, H. SINGH, T. R. BHARDWAJ, D. PAUL

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Nine analogues of the azasteroid muscle relaxant chandonium have been tested for neuromuscular blocking activity, ganglion blocking activity, inhibitory effects on cardiac muscarinic receptors, and for effects on noradrenergic transmission. Experiments were performed in anaesthetized cats and in isolated preparations. The two bisquaternary compounds HS‐626 and HS‐627, choline and acetylcholine‐like analogues of chandonium respectively, were approximately equipotent with chandonium as neuromuscular blocking agents in the cat, but HS‐672 possessed slightly more vagal blocking action. No evidence was obtained for ganglion block. The monoquaternary analogues, HS‐408 and HS‐465 and two 4‐aza‐androstanes, (HS‐522 and HS‐523) were more than 100 times less active than the bisquaternary compounds as neuromuscular blocking agents, and produced vagal blockade and ganglion blockade at sub‐neuromuscular blocking doses. pA2 determinations in the chick biventer cervicis muscle, the guinea‐pig atria and guinea‐pig ileum showed that the bisquaternary compounds chandonium, HS‐626 and HS‐627 were much more potent in blocking cardiac than intestinal muscarinic receptors and that HS‐626 possessed the widest margin between concentrations blocking the nicotinic receptors at the neuromuscular junction and the cardiac muscarinic receptors. Evidence for the three bisquaternary compounds blocking neuronal noradrenaline reuptake was obtained only at very high concentrations. HS‐626 possessed a slightly more desirable spectrum of activities than chandonium, but the degree of improvement over the parent compound is insufficient to merit extensive clinical testing.

Original languageEnglish
Pages (from-to)451-457
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Volume33
Issue number1
DOIs
Publication statusPublished - 1 Jan 1981

Fingerprint

Azasteroids
Autonomic Agents
Muscarinic Receptors
Choline
Ganglia
Acetylcholine
Neuromuscular Blocking Agents
Cats
Muscles
Neuromuscular Junction
Nicotinic Receptors
Ileum
Cholinergic Agents
Norepinephrine

Keywords

  • acetylcholine
  • atropine
  • azasteroid
  • chandonium
  • chandonium derivative
  • choline
  • cocaine
  • ganglion blocking agent
  • hexamethonium
  • muscarinic receptor
  • noradrenalin
  • pentobarbital
  • reserpine
  • animal experiment
  • autonomic nervous system
  • digestive system
  • dose response
  • drug comparison
  • drug response
  • heart muscle
  • intestine
  • neuromuscular blocking
  • neuromuscular transmission
  • peripheral nervous system

Cite this

@article{5550797216264ecbab5e592ccf29dc7d,
title = "The neuromuscular and autonomic blocking effects of azasteroids containing choline or acetylcholine fragments",
abstract = "Nine analogues of the azasteroid muscle relaxant chandonium have been tested for neuromuscular blocking activity, ganglion blocking activity, inhibitory effects on cardiac muscarinic receptors, and for effects on noradrenergic transmission. Experiments were performed in anaesthetized cats and in isolated preparations. The two bisquaternary compounds HS‐626 and HS‐627, choline and acetylcholine‐like analogues of chandonium respectively, were approximately equipotent with chandonium as neuromuscular blocking agents in the cat, but HS‐672 possessed slightly more vagal blocking action. No evidence was obtained for ganglion block. The monoquaternary analogues, HS‐408 and HS‐465 and two 4‐aza‐androstanes, (HS‐522 and HS‐523) were more than 100 times less active than the bisquaternary compounds as neuromuscular blocking agents, and produced vagal blockade and ganglion blockade at sub‐neuromuscular blocking doses. pA2 determinations in the chick biventer cervicis muscle, the guinea‐pig atria and guinea‐pig ileum showed that the bisquaternary compounds chandonium, HS‐626 and HS‐627 were much more potent in blocking cardiac than intestinal muscarinic receptors and that HS‐626 possessed the widest margin between concentrations blocking the nicotinic receptors at the neuromuscular junction and the cardiac muscarinic receptors. Evidence for the three bisquaternary compounds blocking neuronal noradrenaline reuptake was obtained only at very high concentrations. HS‐626 possessed a slightly more desirable spectrum of activities than chandonium, but the degree of improvement over the parent compound is insufficient to merit extensive clinical testing.",
keywords = "acetylcholine, atropine, azasteroid, chandonium, chandonium derivative, choline, cocaine, ganglion blocking agent, hexamethonium, muscarinic receptor, noradrenalin, pentobarbital, reserpine, animal experiment, autonomic nervous system, digestive system, dose response, drug comparison, drug response, heart muscle, intestine, neuromuscular blocking, neuromuscular transmission, peripheral nervous system",
author = "MARSHALL, {I. G.} and HARVEY, {A. L.} and H. SINGH and BHARDWAJ, {T. R.} and D. PAUL",
year = "1981",
month = "1",
day = "1",
doi = "10.1111/j.2042-7158.1981.tb13831.x",
language = "English",
volume = "33",
pages = "451--457",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
number = "1",

}

The neuromuscular and autonomic blocking effects of azasteroids containing choline or acetylcholine fragments. / MARSHALL, I. G.; HARVEY, A. L.; SINGH, H.; BHARDWAJ, T. R.; PAUL, D.

In: Journal of Pharmacy and Pharmacology, Vol. 33, No. 1, 01.01.1981, p. 451-457.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The neuromuscular and autonomic blocking effects of azasteroids containing choline or acetylcholine fragments

AU - MARSHALL, I. G.

AU - HARVEY, A. L.

AU - SINGH, H.

AU - BHARDWAJ, T. R.

AU - PAUL, D.

PY - 1981/1/1

Y1 - 1981/1/1

N2 - Nine analogues of the azasteroid muscle relaxant chandonium have been tested for neuromuscular blocking activity, ganglion blocking activity, inhibitory effects on cardiac muscarinic receptors, and for effects on noradrenergic transmission. Experiments were performed in anaesthetized cats and in isolated preparations. The two bisquaternary compounds HS‐626 and HS‐627, choline and acetylcholine‐like analogues of chandonium respectively, were approximately equipotent with chandonium as neuromuscular blocking agents in the cat, but HS‐672 possessed slightly more vagal blocking action. No evidence was obtained for ganglion block. The monoquaternary analogues, HS‐408 and HS‐465 and two 4‐aza‐androstanes, (HS‐522 and HS‐523) were more than 100 times less active than the bisquaternary compounds as neuromuscular blocking agents, and produced vagal blockade and ganglion blockade at sub‐neuromuscular blocking doses. pA2 determinations in the chick biventer cervicis muscle, the guinea‐pig atria and guinea‐pig ileum showed that the bisquaternary compounds chandonium, HS‐626 and HS‐627 were much more potent in blocking cardiac than intestinal muscarinic receptors and that HS‐626 possessed the widest margin between concentrations blocking the nicotinic receptors at the neuromuscular junction and the cardiac muscarinic receptors. Evidence for the three bisquaternary compounds blocking neuronal noradrenaline reuptake was obtained only at very high concentrations. HS‐626 possessed a slightly more desirable spectrum of activities than chandonium, but the degree of improvement over the parent compound is insufficient to merit extensive clinical testing.

AB - Nine analogues of the azasteroid muscle relaxant chandonium have been tested for neuromuscular blocking activity, ganglion blocking activity, inhibitory effects on cardiac muscarinic receptors, and for effects on noradrenergic transmission. Experiments were performed in anaesthetized cats and in isolated preparations. The two bisquaternary compounds HS‐626 and HS‐627, choline and acetylcholine‐like analogues of chandonium respectively, were approximately equipotent with chandonium as neuromuscular blocking agents in the cat, but HS‐672 possessed slightly more vagal blocking action. No evidence was obtained for ganglion block. The monoquaternary analogues, HS‐408 and HS‐465 and two 4‐aza‐androstanes, (HS‐522 and HS‐523) were more than 100 times less active than the bisquaternary compounds as neuromuscular blocking agents, and produced vagal blockade and ganglion blockade at sub‐neuromuscular blocking doses. pA2 determinations in the chick biventer cervicis muscle, the guinea‐pig atria and guinea‐pig ileum showed that the bisquaternary compounds chandonium, HS‐626 and HS‐627 were much more potent in blocking cardiac than intestinal muscarinic receptors and that HS‐626 possessed the widest margin between concentrations blocking the nicotinic receptors at the neuromuscular junction and the cardiac muscarinic receptors. Evidence for the three bisquaternary compounds blocking neuronal noradrenaline reuptake was obtained only at very high concentrations. HS‐626 possessed a slightly more desirable spectrum of activities than chandonium, but the degree of improvement over the parent compound is insufficient to merit extensive clinical testing.

KW - acetylcholine

KW - atropine

KW - azasteroid

KW - chandonium

KW - chandonium derivative

KW - choline

KW - cocaine

KW - ganglion blocking agent

KW - hexamethonium

KW - muscarinic receptor

KW - noradrenalin

KW - pentobarbital

KW - reserpine

KW - animal experiment

KW - autonomic nervous system

KW - digestive system

KW - dose response

KW - drug comparison

KW - drug response

KW - heart muscle

KW - intestine

KW - neuromuscular blocking

KW - neuromuscular transmission

KW - peripheral nervous system

UR - http://www.scopus.com/inward/record.url?scp=0019793703&partnerID=8YFLogxK

U2 - 10.1111/j.2042-7158.1981.tb13831.x

DO - 10.1111/j.2042-7158.1981.tb13831.x

M3 - Article

VL - 33

SP - 451

EP - 457

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 1

ER -