?Alternative? effects of local anesthetic agents

Pecher, Sabine; Böttiger, Bernd W.; Graf, Bernhard M.; Hollmann, Markus W.

doi:10.1007/s00101-003-0629-1

Cited by 12 publications

(3 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These new findings coincided with further reports on a variety of different clinical effects of LAs, such as anti-inflammatory , Cassuto, Sinclair et al 2006), anti-thrombotic (Lo, Honemann et al 2001), or immunomodulatory (Cassuto, Sinclair et al 2006) activities. These LA features were referred to as "alternative effects" (Pecher, Bottiger et al 2004). Obviously, LAs possess a much broader spectrum of clinically important properties, extending far beyond their pure analgesic action.…”

Section: Diversity Of Molecular Targets Of Local Anestheticsmentioning

confidence: 99%

Membrane-Mediated Activity of Local Anesthetics

et al. 2021

View full text Add to dashboard Cite

The activity of local anesthetics (LAs) has been attributed to the inhibition of ion channels, causing anesthesia. However, there is a growing body of research showing that LAs act on a wide range of receptors and channel proteins, far beyond simple analgesia. The current concept of ligand recognition may no longer explain the multitude of protein targets influenced by LAs.We hypothesize that LAs can cause anesthesia without directly binding to the receptor proteins, just by changing the physical properties of the lipid bilayer surrounding these proteins and ion channels, based on LAs' amphiphilicity. It is possible that LAs act in one of the following ways: they (a) dissolve raft-like membrane micro-domains, (b) impede nerve impulse propagation by lowering the lipid phase transition temperature, or (c) modulate the lateral pressure profile of the lipid bilayer. This could also explain the numerous additional effects of LA besides anesthesia.Furthermore, the concepts of membrane-mediated activity and binding to ion channels do not have to exclude each other. If we were to consider LA as the middle part of a continuum, between unspecific membrane mediated activity on one end, and highly specific ligand binding on the other end, we could describe LA as the link between the unspecific action of general anesthetics, and toxins with their highly specific receptor binding. This comprehensive membrane-mediated model offers a fresh perspective to clinical and pharmaceutical research and therapeutic applications of local anesthetics.

show abstract

Section: Diversity Of Molecular Targets Of Local Anestheticsmentioning

confidence: 99%

Membrane-Mediated Activity of Local Anesthetics

et al. 2021

View full text Add to dashboard Cite

show abstract

“…LA'lerin, uyarılamayan hücreler üzerinde, sodium iyon kanalındaki ilacın yarı ömründen daha uzun süren pleiotropikal (alternative etkiler) etkileri olduğuna dair kanıtlar vardır (7,8).…”

Section: Bilimsel Kanıtlarunclassified

“…LA'lerin, uyarlamayan hücreler üzerinde, sodium iyon kanalndaki ilacn yar ömründen daha uzun süren pleiotropikal (alternative etkiler) etkileri olduğuna dair kantlar vardr. [7,8] Baz çalşmalarda nöral terapiye dair ilave moleküler mekanizmalar gösterilmiştir. I -----------1 ----------1 ----------1 ---------1 ----------1 ----------1 ---------1 ---------- Lokal anestezikler Gq-protein-kompleksi bağml hücre içi antiinflamatuar mekanizmalar tetiklemekte [9], aşr aktif granülositleri deaktive etmekte, NMDA reseptörleri üzerinden sinyal iletimini basklamakta [10], eikasanoidler, histamin, prostaglandin ve sitokinler gibi antiinflamatuar mediatörlerin sentez ve salnmn etkilemektedir.…”

Section: Bilimsel Kanıtlarunclassified