Paradoxical neostigmine-induced TOFfade: On the role of presynaptic cholinergic and adenosine receptors

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Ramos, ED (Author) Other; Antonio, MB (Author) Other; Ambiel, CR (Author) Other; Paulo Correia de Sá (Author) ICBAS; Alves Do Prado, W (Author) Other

Journal

Title: European Journal of Pharmacology

Vol. 723

Pages: 389-396

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00F-ZY8

DOI: 10.1016/j.ejphar.2013.11.001

Abstract (EN): Neuromuscular transmission is clinically monitored using the train-of-four ratio (TOFratio), which is the quotient between twitch tension produced by the fourth (T-4) and by the first (T-1) stimulus within a train-of-four stimulation at 2 Hz. Neostigmine causes a paradoxical depression of the TOFratio (TOFfade) that is amplified by intra-arterial atropine in cats. This led us to question the usefulness of the TOFratio as a sole testing element to control neostigmine-induced reversal of neuromuscular transmission block caused by non depolarizing agents. We hypothesized that the inhibition of cholinesterase activity might increase acetylcholine bioavailability and consequently cholinoceptor activation, leading to concomitant adenosine release from nerve endings and skeletal muscle fibers. The involvement of presynaptic muscarinic and adenosine receptors in neostigminc-induced TOFfade in the rat phrenic nerve diaphragm was investigated. Blockade of adenosine A(2A) receptors with ZM241385 and of rnuscarinic M-2 receptors with methoctramine or atropine amplified neostigmine-induced TOFfade. Notwithstanding TOFfade amplification, the blockade of M-2 or A(2A) receptors increased both T-1 and T-4 twitch tensions above control during the first 3 min of neostigmine application. Beyond that period, the T-1 twitch tension returned to baseline, whereas T-4 decreased further until the control value with neostigmine alone. Blockade of M-1 receptors by pirenzepine did not change neostigmine-induced TOFfade,, unless A(2A) receptors were concurrently blocked with ZM241385. Data indicate that the paradoxical neostigmine-induced fade involves presynaptic mechanisms that regulate transmitter release and synaptic adenosine accumulation, including the activation of adenosine A(2A),4 and muscarinic M2 receptors. (C) 2013 Elsevier B.V. All tights reserved

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8