Species variation in the site and mechanism of the neuromuscular effects of diadonium in rodents.
The unusually wide, 80-fold species variation observed by others (1,2) in the neuromuscular (NM) potency of diadonium, a nondepolarizing muscle relaxant (MR), between cat and man suggested that the site and mechanism of its NM effect may vary in different species. To obtain information on this question, the NM potency of diadonium and the reversibility of its NM effect by neostigmine and/or 4-aminopyridine (4AP) was investigated on the in vitro phrenic nerve--hemidiaphragm preparations of rats, mice and guinea pigs. The concentration of diadonium that caused 90% NM block (IC90) was much greater in guinea pigs, 1.74 +/- 0.02 and 1.28 +/- 0.01 mu, when the preparations were stimulated with single stimuli at 0.1 Hz or with 0.1 s trains of 50 Hz tetani every 10 s, respectively, than in rats (IC90 = 62.4 +/- 0.89 and 52.1 +/- 1.00 microM) or mice (IC90 = 51.9 +/- 0.98 and 44.4 +/- 0.22 microM). In guinea pigs, the NM blocking effect of diadonium could be antagonized by neostigmine. This indicates that in this species the NM blocking effect of diadonium is primarily caused by inhibition of the interaction of acetylcholine (ACh), released by the nerve impulse, with the cholinergic receptors (cholinoceptors) of the postjunctional membrane (p.j.m.). By contrast, in rats and mice diadonium was not antagonized by neostigmine but was reversed by 4-aminopyridine. This suggests that in these species, in contrast to other nondepolarizing MR, diadonium does not inhibit NM transmission postsynaptically, but by inhibiting the positive nicotinic feedback mechanism of mobilization of ACh from reserve depots to release sites, causes a presynaptic NM block.(ABSTRACT TRUNCATED AT 250 WORDS)
Foldes
F F
FF
Department of Anesthesiology, University of Miami School of Medicine, Florida.
Chaudhry
I A
IA
Barakat
T
T
Flores
C A
CA
Kinjo
M
M
Bikhazi
G B
GB
Nagashima
H
H
D000109:Acetylcholine / Q000378:metabolism; D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D009125:Muscle Relaxants, Central; D000644:Quaternary Ammonium Compounds; C013473:diadonium; D009388:Neostigmine; D000109:Acetylcholine; D000218:Adamantane