Tonic Blocking Action of Meperidine on Na+and K+Channels in Amphibian Peripheral Nerves

Bräu, Michael E.; Koch, E. Dietlind; Vogel, Werner; Hempelmann, G.

doi:10.1097/00000542-200001000-00026

Cited by 33 publications

(24 citation statements)

References 23 publications

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“…23 Alternatively, nonspecific opioid activity could occur in Na + channels, through molecular mechanisms different from those occasioned by LA. 24 Regarding previous attempts at pharmacological associations, the combination of a centrally acting drug (COD) with a peripherally acting drug (LA) supports the idea that drugs with actions that involve uniting central and peripheral pathways generate onset times, activity durations and various sites of drug action that could increase the analgesic capacity; moreover, these additive and synergistic effects could occur at lower doses. 25 Both COD and LA have hydroxyl groups on a molecular chain attached to the benzene ring.…”

Section: Discussionmentioning

confidence: 88%

Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

et al. 2013

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Opioids are central analgesics that act on the CNS (central nervous system) and PNS (peripheral nervous system). We investigated the effects of codeine (COD) and tramadol (TRAM) on local anesthesia of the sciatic nerve. Eighty Wistar male rats received the following SC injections in the popliteal fossa: local anesthetic with epinephrine (LA); local anesthetic without vasoconstrictor (LA WV); COD; TRAM; LA + COD; LA + TRAM; COD 20 minutes prior to LA (COD 20' + LA) or TRAM 20 minutes prior to LA (TRAM 20' + LA). As a nociceptive function, the blockade was considered the absence of a paw withdraw reflex. As a motor function, it was the absence of claudication. As a proprioceptive function, it was the absence of hopping and tactile responses. All data were compared using repeated-measures analysis of variance (ANOVA). Opioids showed a significant increase in the level of anesthesia, and the blockade duration of LA + COD was greater than that of the remaining groups (p < 0.05). The associated use of opioids improved anesthesia efficacy. This could lead to a new perspective in controlling dental pain.

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Section: Discussionmentioning

confidence: 88%

Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

et al. 2013

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“…The effective concentrations of U50,488 compounds are comparable to the local anesthetic lidocaine for inhibiting sodium channels in amphibian peripheral nerves (half-maximal inhibitory concentration, IC 50 , 172 M) (Bräu et al 2000) and recombinant voltage-dependent sodium channels (IC 50 , 1.9 mM) (Wagner et al 1999).…”

Section: Mechanism Of U50488 Induced Suppression Of Pelvic Nerve Actmentioning

confidence: 99%

Sodium Channel Blocking Actions of the κ-Opioid Receptor Agonist U50,488 Contribute to Its Visceral Antinociceptive Effects

Joshi

Kardos

et al. 2002

Journal of Neurophysiology

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. Sodium channel blocking actions of the -opioid receptor agonist U50,488 contribute to its visceral antinociceptive effects. J Neurophysiol 87: 1271-1279, 2002; 10.1152/jn.00624.2001. The goal of the present study was to determine whether the -opioid receptor agonist (ORA) U50,488 attenuates behavioral and primary afferent nerve responses to noxious colorectal distension (CRD) by sodium channel blockade. We tested the analgesic -ORA (Ϯ)-trans U50,488, its enantiomers (Ϫ)-trans (1S,2S)-U50,488 and non -ORA (ϩ)-trans (1R,2R)-U50,488, and/or its diastereomer (Ϫ)-cis (1S,2R)-U50,488 for their ability to attenuate visceromotor and pelvic nerve afferent fiber responses to noxious CRD in vivo and voltage-activated sodium current in colon sensory neurons in vitro. In unanesthetized rats, subcutaneous administration of U50,488, (1S,2S)-U50,488, and (1R,2R)-U50,488 attenuated the behavioral visceromotor response to noxious CRD; the rank order of potency was: (1S,2S)-U50,488 Ͼ U50,488 Ͼ Ͼ (1R,2R)-U50,488. U50,488 and its stereoisomers also inhibited responses of decentralized pelvic nerve afferent fibers to noxious CRD in a dose-dependent manner. Cumulative doses of 16 mg/kg of (1S,2S)-U50,488, (1S,2R)-U50,488, and (1R,2R)-U50,488 reduced responses to a mean 29, 30, and 47% of control, respectively. The mean inhibitory doses of these drugs were not different (range: 6.6 -10.8 mg/kg). Sodium channel blockers mexiletine and carbamazepine mimicked the effect of U50,488. In contrast, the -ORAs dynorphin (1-13) and ICI 204,488 were ineffective in attenuating pelvic nerve activity. Perfusion of (1S,2S)-U50,488, (1S,2R)-U50,488, or (1R,2R)-U50,488 on colon sensory neurons in vitro decreased voltage-activated sodium currents. This inhibition by U50,488 and its stereoisomers was not opioid receptor-mediated because it could not be reversed by the opioid receptor antagonist naloxone and was also not a G protein-mediated effect. The results reported here suggest that the visceral antinociceptive effects of U50,488 and its stereoisomers are contributed to by their peripheral sodium channel blocking actions. I N T R O D U C T I O NThe mechanisms and modulation of visceral pain have been extensively examined using colorectal distension (CRD) as a noxious visceral stimulus. Previous studies employing CRD have documented the ability of -opioid receptor agonists (ORAs) like U50,488 to attenuate pseudaffective visceromotor and cardiovascular responses to noxious CRD following their systemic, but not intrathecal administration (Danzebrink et al. 1995; Harada et al. 1995a,b). A peripheral, visceral antinociceptive action of U50,488 has been demonstrated. U50,488 was shown to dose dependently inhibit responses of mechanosensitive pelvic nerve afferent fibers to noxious colorectal or urinary bladder distension in the rat Su et al. 1997a,b). This inhibition could not be completely antagonized by very high doses of naloxone or by two -opioid receptor-selective antagonists, nor-Binaltorphimine dihydrochloride (nor-BNI) and DIPPA. Furthermore, ...

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“…Este mecanismo de ação é dependente do pH do meio e da concentração presente de tramadol (Mert et al, 2002b), o qual age mais intensamente nos canais de potássio (responsáveis pela repolarização) do que nos de sódio (responsáveis pela despolarização). Este mecanismo é similar à meperidina, que também age em canais de potássio de nervos periféricos (Brau et al, 2000). O mecanismo pelo qual o tramadol induz vômito não é muito bem definido.…”

Section: Mepivacaínaunclassified

“…A duração do efeito anestésico observada em ambos os grupos está de acordo com a duração do efeito anestésico verificado no estudo de Porto et al (2007) entre três e quatro horas. Este resultado deve-se ao desenho do estudo e ao provável mecanismo de ação do tramadol nos canais de sódio (Tsai et al, 2001;Mert et al, 2006) ou de potássio de neurônios periféricos (Brau et al, 2000). O cloridrato de tramadol foi aplicado no interior do alvéolo e na submucosa adjacente ao local da exodontia após o término do procedimento, tempo este em que a ação do anestésico já era plena, com a ligação aos canais iônicos do neurônio aferente em curso, sem possibilidade de o tramadol incrementar tal efeito, pois seus sítios de ligação já estavam ocupados com um agente anestésico local de longa duração de efeitos.…”

Section: Ordemunclassified

“…Clonidina, antidepressivos e opioides (Strumper;Duriex, 2004), incluindo o tramadol (Kapral et al, 1999;Robaux et al, 2004) (Collins et al, 1997). Também é uma alternativa aos indivíduos em que a associação analgésica de codeína e acetaminofen não é bem tolerada ou contraindicada (Moore, 1999 (Brau et al, 2000). Este efeito local não pode ser revertido pela naloxona (Tsai et al, 2001), o que comprova a presença de um mecanismo local independente da ação nos receptores opioides da medula vertebral.…”

Section: Ordemunclassified

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Eficácia analgésica pós-operatória e ação anestésica adjuvante do cloridrato de tramadol utilizado localmente após exodontias de terceiros molares inferiores impactados

Ceccheti¹

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AGRADECIMENTOSÀ Profa. Dra. Maria da Graça Naclério-Homem, por acreditar sempre em meu potencial, pelo incentivo e apoio nessa jornada de 15 anos pós-graduação. Sua presença em minha vida trouxe oportunidades e desafios superados com grande alegria.À Profa. Maria Paula Siqueira de Melo Peres, por promover o ensino, a pesquisa e assistência na minha segunda casa, o Hospital das Clínicas. Obrigado pelo incentivo constante ao meu desenvolvimento. Foi estudado o efeito analgésico e anestésico adjuvante do cloridrato de tramadol aplicado localmente, após extração do terceiro molar inferior impactado. Um total de 52 pacientes foi submetido à exodontia sob anestesia local (mepivacaína 2% 1:20 000 corbadrina), em estudo duplo-cego, dose única, cruzado, controlado por placebo. Pacientes e os lados dos procedimentos foram distribuídos aleatoriamente para receberem 2 ml de tramadol (100%) (grupo T) ou 2 ml de solução salina 0,9% (grupo P). Ambas as soluções foram injetadas na submucosa gengival e alvéolo, imediatamente após as cirurgias realizadas por um mesmo cirurgião. Impacção dental e quantidade anestésica foram pareadas. Dados do consumo e a hora de uso The present study sought to assess the analgesic and adjuvant anesthetic effects of surgical site administration of tramadol hydrochloride immediately after extraction of impacted mandibular third molars. In this double-blind, placebo-controlled, singledose, crossover investigation, 52 patients underwent bilateral extraction of impacted mandibular third molars under local anesthesia (mepivacaine 2% with levonordefrin 1:20 000). Patients and procedures, by side of intervention, were randomly assigned to receive either 2 mL of tramadol (100%) (Group T, n = 52) or 2 mL of normal saline, 0.9% (Group P, n = 52). Medications were administered by submucosal injection at the level of the third molar immediately after surgery. All patients were operated on by the same surgeon; patients were paired for technical difficulty and amount of anesthetic solution. Use of supplementary analgesics (500 mg metamizole) and time to first postoperative use of a rescue drug were used to assess the analgesic effect of tramadol. Pain level on both sides (Group T and P) was recorded on a visual analog scale (VAS 0-10 cm) immediately after cessation of anesthetic effect and at 4, 8, 24, 48, and 72 hours postoperatively. Data were compared using the Wilcoxon test (p < 0.05). There was no difference in anesthetic blockade between groups. There were no differences in reported adverse effects. In the 72 hours following surgery, patients in group T took significantly fewer (p = 0.008) metamizole tablets (3.37 ± 4.65) than did those in group P (4.4 ± 3.71). Time to first dose of a rescue drug (in minutes) was longer in Group T (303.72 ± 416.01) than in Group P (185.4 ± 59.4) (p = 0.006).Tramadol reduced pain intensity values (VAS) significantly in Group T (3.55 ± 2.27) as compared to Group P (5.26 ± 2.49) after anesthetic effect had worn off (p = 0.001). Local administration of tramadol after oral surg...

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Tonic Blocking Action of Meperidine on Na+and K+Channels in Amphibian Peripheral Nerves

Abstract: It is concluded that meperidine has a nonselective inhibitory action on Na+ and K+ channels of amphibian peripheral nerve. For tonic Na+ channel block, neither an opioid receptor nor the the local anesthetic agent binding site is the target site for meperidine block.

Cited by 33 publications

References 23 publications

Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

Sodium Channel Blocking Actions of the κ-Opioid Receptor Agonist U50,488 Contribute to Its Visceral Antinociceptive Effects

Eficácia analgésica pós-operatória e ação anestésica adjuvante do cloridrato de tramadol utilizado localmente após exodontias de terceiros molares inferiores impactados

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