The effects of dihydrochandonium and other chandonium analogues on neuromuscular and autonomic transmission

P. T. APONG, I. G. MARSHALL, A. L. HARVEY, HARKISHAN SINGH, DHARAM PAUL, T. R. BHARDWAJ, N. K. AHUJA

Research output: Contribution to journalArticle

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Abstract

The muscle relaxant chandonium and four of its analogues have been assessed for neuromuscular, ganglion blocking and vagolytic activity in the chloralose‐anaesthetized cat, for neuromuscular blocking activity in the chick isolated biventer cervicis and rat phrenic nerve‐hemidiaphragm preparations, for muscarinic and histamine blocking activity in the guinea‐pig isolated ileum preparation and for effects on adrenergic responses in the rat isolated vas deferens preparation. All five compounds produced neuromuscular block of rapid onset and short duration when given to cats in doses of 5–500 μg kg−1 and produced non‐depolarizing competitive neuromuscular blockade in the isolated skeletal muscle preparations. Saturation of the 5–6 androstene bond to produce dihydrochandonium (HS692) resulted in a loss of potency by a factor of 0·5. The NN‐diethyl analogue of dihydrochandonium (HS693) was about half as potent as HS692. The triethyl (HS704) and NN‐diethyl (HS705) analogues of chandonium possessed one‐tenth and one‐fifth respectively of the muscle relaxant activity of chandonium. In cats, all compounds inhibited the bradycardia produced by vagal stimulation and by methacholine, the vagolytic effect of HS693 being particularly powerful and long‐lasting. Although the compounds did not block the depressor response to methacholine in vivo, all the compounds inhibited responses to carbachol in the guinea‐pig isolated ileum. However, from pA2 values the compounds were found to be 10–100 times more active at nicotinic than at muscarinic receptors. None of the compounds had histamine‐blocking activity, ganglion‐blocking activity, or actions on adrenergic responses.

LanguageEnglish
Pages521-528
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume31
Issue number1
DOIs
Publication statusPublished - 1 Jan 1979

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Neuromuscular Blockade
Cats
Methacholine Chloride
Ileum
Ganglia
Adrenergic Agents
Histamine
Guinea Pigs
Androstenes
Muscles
Chloralose
Phrenic Nerve
Vas Deferens
Carbachol
Muscarinic Receptors
Bradycardia
Cholinergic Agents
Skeletal Muscle
dihydrochandonium

Keywords

  • 1,1 dimethyl 4 phenylpiperazinium
  • 3,4 diaminopyridine
  • 3alpha dihydrochandonium iodide
  • 4 aminopyridine
  • 5,5' dithiobis(2 nitrobenzoic acid)
  • acetylcholine
  • acetylthiocholine
  • atropine
  • animal experiment
  • autonomic nervous system
  • biventer cervicis muscle
  • blood and hemopoietic system
  • cardiovascular system
  • drug administration
  • neuromuscular blocking
  • neuromuscular transmission

Cite this

APONG, P. T. ; MARSHALL, I. G. ; HARVEY, A. L. ; SINGH, HARKISHAN ; PAUL, DHARAM ; BHARDWAJ, T. R. ; AHUJA, N. K. / The effects of dihydrochandonium and other chandonium analogues on neuromuscular and autonomic transmission. In: Journal of Pharmacy and Pharmacology. 1979 ; Vol. 31, No. 1. pp. 521-528.
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The effects of dihydrochandonium and other chandonium analogues on neuromuscular and autonomic transmission. / APONG, P. T. ; MARSHALL, I. G.; HARVEY, A. L.; SINGH, HARKISHAN; PAUL, DHARAM; BHARDWAJ, T. R.; AHUJA, N. K.

In: Journal of Pharmacy and Pharmacology, Vol. 31, No. 1, 01.01.1979, p. 521-528.

Research output: Contribution to journalArticle

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T1 - The effects of dihydrochandonium and other chandonium analogues on neuromuscular and autonomic transmission

AU - APONG, P. T.

AU - MARSHALL, I. G.

AU - HARVEY, A. L.

AU - SINGH, HARKISHAN

AU - PAUL, DHARAM

AU - BHARDWAJ, T. R.

AU - AHUJA, N. K.

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N2 - The muscle relaxant chandonium and four of its analogues have been assessed for neuromuscular, ganglion blocking and vagolytic activity in the chloralose‐anaesthetized cat, for neuromuscular blocking activity in the chick isolated biventer cervicis and rat phrenic nerve‐hemidiaphragm preparations, for muscarinic and histamine blocking activity in the guinea‐pig isolated ileum preparation and for effects on adrenergic responses in the rat isolated vas deferens preparation. All five compounds produced neuromuscular block of rapid onset and short duration when given to cats in doses of 5–500 μg kg−1 and produced non‐depolarizing competitive neuromuscular blockade in the isolated skeletal muscle preparations. Saturation of the 5–6 androstene bond to produce dihydrochandonium (HS692) resulted in a loss of potency by a factor of 0·5. The NN‐diethyl analogue of dihydrochandonium (HS693) was about half as potent as HS692. The triethyl (HS704) and NN‐diethyl (HS705) analogues of chandonium possessed one‐tenth and one‐fifth respectively of the muscle relaxant activity of chandonium. In cats, all compounds inhibited the bradycardia produced by vagal stimulation and by methacholine, the vagolytic effect of HS693 being particularly powerful and long‐lasting. Although the compounds did not block the depressor response to methacholine in vivo, all the compounds inhibited responses to carbachol in the guinea‐pig isolated ileum. However, from pA2 values the compounds were found to be 10–100 times more active at nicotinic than at muscarinic receptors. None of the compounds had histamine‐blocking activity, ganglion‐blocking activity, or actions on adrenergic responses.

AB - The muscle relaxant chandonium and four of its analogues have been assessed for neuromuscular, ganglion blocking and vagolytic activity in the chloralose‐anaesthetized cat, for neuromuscular blocking activity in the chick isolated biventer cervicis and rat phrenic nerve‐hemidiaphragm preparations, for muscarinic and histamine blocking activity in the guinea‐pig isolated ileum preparation and for effects on adrenergic responses in the rat isolated vas deferens preparation. All five compounds produced neuromuscular block of rapid onset and short duration when given to cats in doses of 5–500 μg kg−1 and produced non‐depolarizing competitive neuromuscular blockade in the isolated skeletal muscle preparations. Saturation of the 5–6 androstene bond to produce dihydrochandonium (HS692) resulted in a loss of potency by a factor of 0·5. The NN‐diethyl analogue of dihydrochandonium (HS693) was about half as potent as HS692. The triethyl (HS704) and NN‐diethyl (HS705) analogues of chandonium possessed one‐tenth and one‐fifth respectively of the muscle relaxant activity of chandonium. In cats, all compounds inhibited the bradycardia produced by vagal stimulation and by methacholine, the vagolytic effect of HS693 being particularly powerful and long‐lasting. Although the compounds did not block the depressor response to methacholine in vivo, all the compounds inhibited responses to carbachol in the guinea‐pig isolated ileum. However, from pA2 values the compounds were found to be 10–100 times more active at nicotinic than at muscarinic receptors. None of the compounds had histamine‐blocking activity, ganglion‐blocking activity, or actions on adrenergic responses.

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KW - 3alpha dihydrochandonium iodide

KW - 4 aminopyridine

KW - 5,5' dithiobis(2 nitrobenzoic acid)

KW - acetylcholine

KW - acetylthiocholine

KW - atropine

KW - animal experiment

KW - autonomic nervous system

KW - biventer cervicis muscle

KW - blood and hemopoietic system

KW - cardiovascular system

KW - drug administration

KW - neuromuscular blocking

KW - neuromuscular transmission

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M3 - Article

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JO - Journal of Pharmacy and Pharmacology

T2 - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

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