Time-dependent modulation of muscarinic m1/m3 receptor signalling by local anaesthetics

Abstract

Lidocaine modulates muscarinic m1 and m3 receptors in a time- and Gαq-dependent manner, but this is masked by enhanced PKC activity. The biphasic time course may be due to interactions of LAs with an extracellular receptor domain, modulated by PKC activity. Prolonged exposure to LAs may not benefit pulmonary function, but may positively affect postoperative cognitive function.

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain

“…Lidocaine has a time‐dependent biphasic response on m1 and m3 receptor signalling: Initially, m1 and m3 receptors are inhibited; after 8 hours, m1 and m3 signalling is enhanced. This enhancement may be attributed to an interaction with an extracellular receptor domain and subsequent modulation of PKC activity and receptor phosphorylation (Picardi et al., ).…”

“…Most likely, perioperative administration is sufficient because modulatory action on the inflammatory response primarily takes place during surgery and sustained lidocaine concentrations in cerebrospinal fluid extend beyond infusion time (Tsai et al., ). However, in vitro studies showed a time‐dependent enhancement on GPCR (Hollmann et al., ; Picardi et al., ).…”

Anti-Inflammatory Characteristics of Local Anesthetics: Inhibition of TNF-α Secretion of Lipopolysaccharide-Stimulated Leucocytes in Human Blood Samples

“…LAs influence many different receptors other than sodium ion channels [ 22 , 23 , 24 , 25 , 26 ]. All of these effects may contribute to the many different therapeutic effects of LAs [ 2 ].…”

Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review

“…Both receptor types have been implicated in pain transmission and are potential targets for analgesics. 106,114 Picardi and colleagues 111 and Hollmann and colleagues 115,116 examined the potential blockade of m1 and m3 muscarinic receptors by lidocaine. M1 muscarinic receptor signalling was inhibited with an IC 50 of 18 nM, which is about 1000-fold lower than that for sodium channel blockade (Fig.…”

“…105 Prolonged exposure of m1 and m3 receptors to lidocaine resulted in a biphasic time course with initial inhibition, followed by enhanced signalling. 111 The nAChRs are also targets of lidocaine. Both the muscletype nAChR 117e119 and the neuronal nAChR 117,120 are inhibited with an IC 50 in a low micromolar range (Fig.…”