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Journal of Anesthesia

, 23:513 | Cite as

Presynaptic M1, M2, and A1 receptors play roles in tetanic fade induced by pancuronium or cisatracurium

  • Elaine Campana Sanches Bornia
  • Érika Bando
  • Miguel MachinskiJr
  • Monalisa Wolski Pereira
  • Wilson Alves-Do-Prado
Original Article

Abstract

Purpose

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 µM for hexamethonium (26.8 ± 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 ± 2.55% fade), 0.32 µM for pancuronium (25.4 ± 2.2% fade), and 0.32 µM for cisatracurium (24.7 ± 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 µM, 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 µM) showed antiacetylcholinesterase activity (in plasma, 14.2 ± 1.6%; 6%; in erythrocyt 17.2 ± 2.66%) similar to that of pancuronium (0.32 µM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium.

Conclusion

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.

Key words

Pancuronium Cisatracurium Pirenzepine Methoctramine 

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Copyright information

© Japanese Society of Anesthesiologists 2009

Authors and Affiliations

  • Elaine Campana Sanches Bornia
    • 1
  • Érika Bando
    • 2
  • Miguel MachinskiJr
    • 2
  • Monalisa Wolski Pereira
    • 1
  • Wilson Alves-Do-Prado
    • 1
    • 3
  1. 1.Department of PharmacologyState University of MaringaParanáBrazil
  2. 2.Department of Clinical Analysis and ToxicologyState University of MaringaParanáBrazil
  3. 3.Laboratory of Pharmacology of Neuromuscular TransmissionUniversidade Estadual de MaringáMaringáBrazil

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