Local Anesthetics Have Different Mechanisms and Sites of Action at Recombinant 5-HT3 Receptors

Ueta, Kazuyoshi; Suzuki, Takahiro; Sugimoto, Masahiro; Uchida, Ichirō; Mashimo, Takashi

doi:10.1016/j.rapm.2007.06.391

Cited by 18 publications

(13 citation statements)

References 26 publications

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“…When administrated to fish via bath immersion, they enter the circulation and produce general anaesthesia by inhibiting neural signal transmission ranging from the periphery to higher parts of the nervous system. The precise mechanism of action in the central nervous system is not fully understood (Hara and Sata 2007;Hedrick and Winmill 2003;Ueta et al 2007). Many of the adverse effects caused by this class of drugs in man are related to effects on the CNS and the cardiovascular system (Rang et al 2003).…”

Section: Metacaine and Benzocainementioning

confidence: 99%

Anaesthesia of farmed fish: implications for welfare

Zahl

Samuelsen

Kiessling

2011

Fish Physiol Biochem

269

188

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During their life cycle as farmed animals, there are several situations in which fish are subjected to handling and confinement. Netting, weighing, sorting, vaccination, transport and, at the end, slaughter are frequent events under farming conditions. As research subjects, fish may also undergo surgical procedures that range from tagging, sampling and small incisions to invasive procedures. In these situations, treatment with anaesthetic agents may be necessary in order to ensure the welfare of the fish. The main objective of this paper is to review our knowledge of the effects of anaesthetic agents in farmed fish and their possible implications for welfare. As wide variations in response to anaesthesia have been observed both between and within species, special attention has been paid to the importance of secondary factors such as body weight, water temperature and acute stress. In this review, we have limited ourselves to the anaesthetic agents such as benzocaine, metacaine (MS-222), metomidate hydrochloride, isoeugenol, 2-phenoxyethanol and quinaldine. Anaesthetic protocols of fish usually refer to one single agent, whereas protocols of human and veterinary medicine cover combinations of several drugs, each contributing to the effects needed in the anaesthesia. As stress prior to anaesthesia may result in abnormal reactions, pre-anaesthetic sedation is regularly used in order to reduce or avoid stress and is an integral part of the veterinary protocols of higher vertebrates. Furthermore, the anaesthetic agents that are used in order to obtain general anaesthesia are combined with analgesic agents that target nociception. The increased use of such combinations in fish is therefore included as a special section. Anaesthetic agents are widely used to avoid stress during various farming procedures. While several studies report that anaesthetics are effective in reducing the stress associated with confinement and handling, there are indications that anaesthesia may in itself induce a stress response, measured by elevated levels of cortisol. MS-222 has been reported to elicit high cortisol release rates immediately following exposure, while benzocaine causes a bimodal response. Metomidate has an inhibitory effect on cortisol in fish and seems to induce the lowest release of cortisol of the agents reported in the literature. Compared to what is observed following severe stressors such as handling and confinement, the amount of cortisol released in response to anaesthesia appears to be low but may represent an extra load under otherwise stressful circumstances. Furthermore, anaesthetics may cause secondary adverse reactions such as acidosis and osmotic stress due to respiratory arrest and insufficient exchange of gas and ions between the blood and the water. All in all, anaesthetics may reduce stress and thereby improve welfare but can also have unwanted side effects that reduce the welfare of the fish and should therefore always be used with caution. Finally, on the basis of the data reported in the literature and o...

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Section: Metacaine and Benzocainementioning

confidence: 99%

Anaesthesia of farmed fish: implications for welfare

Zahl

Samuelsen

Kiessling

2011

Fish Physiol Biochem

269

188

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“…The most accepted hypothesis describes the uncharged form of LA crossing the cellular membrane, while the charged form attaches to the membrane surface [2,[6][7][8]. This attachment is performed via their amino terminal, which is very hydrophilic and cannot cross the water/membrane interface.…”

Section: Introductionmentioning

confidence: 99%

“…In our work, we investigate three of these drugs [1][2][3][4][5][6][7][8], two amino-esters, Tetracaine (TTC) and Benzocaine (BZC), and one amino-amide, Lidocaine (LDC). TTC was selected because it is a powerful, but toxic, local anesthetic, one of the most used in medicine for many years, while LDC is actually the most common amino-amide anesthetic used.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics study of biomembrane/local anesthetics interactions

et al. 2009

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It is still controversial how local anesthetics (LAs) act upon the nervous system and how the membrane contributes to this process, since probably the most important active site of the LAs is located in the sodium channels, a trans-membrane protein. An important role of the bio-membrane would be the stabilization and orientation of local anesthetics molecules, reducing their translational and rotational degrees of freedom, which could reinforce the mechanisms which interrupt the nervous impulse. This study aims to perform a computational analysis of the LAs behaviour in the membrane, and the effect of the water/membrane interface on their stabilization and orientation. Analysis by molecular dynamics (MD) showed that the charged form of these drugs are oriented at the interface, while the neutral form can easily cross the interface, entering the membrane, in agreement with the most recent experimental results in the literature. In contrast, it is here suggested that benzocaine (BZC), which exists only in its uncharged form in physiological media, behaves like the charged anesthetics, remaining stabilized and oriented at the interface. This could explain the similar anesthetic effect of BZC and the charged forms of tetracaine (TTC) and lidocaine (LDC).

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“…While the mechanism of MS-222 is not fully understood, it is known that MS-222 acts as a general anesthetic and it is thought to be effective at blocking nerve conduction by inhibiting voltage-sensitive Na + channels of the central and peripheral nervous systems (Neumcke et al 1981;Arnolds et al 2002;Ueta et al 2007). Thus, extracellular Na + and Ca 2 + were expected to increase and K + was expected to decrease in fish exposed to MS-222 (Sladky et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…It elicits an anesthetic state by depressing the central and peripheral nervous systems (Ferreira et al 1984;Butterworth and Strichartz 1990;Summerfelt and Smith 1990), but the full biochemical process and implications of the effects are not fully understood in fish (Ueta et al 2007). Unfortunately, MS-222 can act as a stressor during induction and throughout the exposure period.…”

mentioning

confidence: 99%

Physiological Stress Responses to Prolonged Exposure to MS‐222 and Surgical Implantation in Juvenile Chinook Salmon

Wagner

Woodley

Seaburg

et al. 2014

N American J Fish Manag

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This study simulated large‐scale monitoring program operations to evaluate the responses of age‐1 Chinook Salmon Oncorhynchus tshawytscha to tricaine methanesulfonate (MS‐222; 80 mg/L) exposure and intracoelomic acoustic microtransmitter implantation. The MS‐222 exposure effects and appropriate exposure times for juvenile Chinook Salmon undergoing intracoelomic implantation were determined using blood analytes (Na+, K+, Ca2+), blood pH, plasma cortisol, and survival immediately following anesthetic exposure (3, 6, 9, and 12 min on day 0) and over a recovery period (days 1, 7, and 14). In addition, effects were examined in surgically implanted and nonimplanted fish (but exposed to MS‐222 for 3 min) over a 14‐d recovery period. Regardless of anesthetic exposure time, there were no mortalities during exposure on day 0 or over the recovery period. On day 0, MS‐222 exposure treatments of 9 and 12 min resulted in significantly higher Na+ and Ca2+ and lower K+, indicating a reduced ability to maintain osmotic balance; however, MS‐222 effectively dampened the cortisol release following surgical implantation and anesthetic exposure. Cortisol concentration was significantly higher in surgically implanted fish than in those not surgically implanted over the recovery period. Given these results, we recommend MS‐222 exposure (80 mg/L) times of 6 min or less for compliance programs and studies involving age‐1 Chinook Salmon. In addition, we recommend for other monitoring programs, regardless of species, that maximum MS‐222 exposure times are implemented to minimize stress and surgical effect and that exposure times are specific to a species’ life stage to prevent overexposure and long‐term effects. Furthermore, the knowledge of effects and the development of maximum exposure times are beneficial for hatchery programs, fish barging or transportation programs, and most studies in which fish behavior and physiological responses would need to be dampened using MS‐222 without adverse side effects. Received January 22, 2014; accepted May 15, 2014

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Local Anesthetics Have Different Mechanisms and Sites of Action at Recombinant 5-HT3 Receptors

Cited by 18 publications

References 26 publications

Anaesthesia of farmed fish: implications for welfare

Anaesthesia of farmed fish: implications for welfare

Molecular dynamics study of biomembrane/local anesthetics interactions

Physiological Stress Responses to Prolonged Exposure to MS‐222 and Surgical Implantation in Juvenile Chinook Salmon

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