Presynaptic M1, M2, and A1 receptors play roles in tetanic fade induced by pancuronium or cisatracurium.
OBJECTIVE
We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade.


METHODS
Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 +/- 3.3 Hz; mean +/- SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated.


RESULTS
The concentrations required for approximately 25% fade were 413 microM for hexamethonium (26.8 +/- 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 +/- 2.55% fade), 0.32 microM for pancuronium (25.4 +/- 2.2% fade), and 0.32 microM for cisatracurium (24.7 +/- 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 microM, attenuated the fade induced by hexamethonium (to 16.0 +/- 2.5% fade), d-tubocurarine (to 6.0 +/- 1.6 fade), pancuronium (to 8.0 +/- 4.0% fade), and cisatracurium (to 11.0 +/- 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 +/- 0.11% fade) and cisatracurium (to 13.3 +/- 5.3% fade). Cisatracurium (0.32 microM) showed antiacetylcholinesterase activity (in plasma, 14.2 +/- 1.6%; 6%; in erythrocyt 17.2 +/- 2.66%) similar to that of pancuronium (0.32 microM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium.


CONCLUSIONS
The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.
Bornia
Elaine Campana Sanches
EC
Department of Pharmacology, State University of Maringa, Paraná, Brazil.
Bando
Erika
E
Machinski
Miguel
M
Pereira
Monalisa Wolski
MW
Alves-Do-Prado
Wilson
W
D000818:Animals; D001279:Atracurium / Q000031:analogs & derivatives* / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D004558:Electric Stimulation; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010197:Pancuronium / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects*; D043643:Receptor, Muscarinic M1 / Q000187:drug effects*; D043585:Receptor, Muscarinic M2 / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
D003959:Diamines; D018727:Muscarinic Antagonists; D003473:Neuromuscular Nondepolarizing Agents; D018733:Nicotinic Antagonists; D043682:Receptor, Adenosine A1; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D014970:Xanthines; D001279:Atracurium; D018738:Hexamethonium; D010890:Pirenzepine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D010197:Pancuronium; C054938:methoctramine; C101584:cisatracurium