The Effect of Meperidine on Thermoregulation in Mice: Involvement of ??2-Adrenoceptors

Abstract

Meperidine has potent antishivering properties. The underlying mechanisms are not fully elucidated, but recent investigations suggest that alpha2-adrenoceptors are likely to be involved. We performed the current study to investigate the effects of meperidine on nonshivering thermogenesis in a model of thermoregulation in mice. After injection (0.1 mL/kg intraperitoneally) of saline, meperidine (20 mg/kg), the specific alpha2-adrenoceptor antagonist atipamezole (2 mg/kg), plus saline or atipamezole plus meperidine, respectively, mice were positioned in a Plexiglas chamber. Rectal temperature and mixed expired carbon dioxide were measured after provoking thermoregulatory effects by whole body cooling. Maximum response intensity of nonshivering thermogenesis and the thermoregulatory threshold for nonshivering thermogenesis, which was defined as the temperature at which a sustained increase in expiratory carbon dioxide can be measured, were investigated. Meperidine significantly decreased the threshold of nonshivering thermogenesis (36.6 degrees C +/- 0.7 degrees C) versus saline (37.9 degrees C +/- 0.6 degrees C) and versus atipamezole plus saline (37.8 degrees C +/- 0.4 degrees C; P <0.01). This effect was abolished after administration of meperidine combined with atipamezole (37.7 degrees C +/- 0.6 degrees C; P <0.05). Meperidine did not decrease the maximum intensity of nonshivering thermogenesis. The results suggest a major role of alpha2-adrenoceptors in the inhibition of thermoregulation by meperidine in mice.

Dexmedetomidine in anaesthesia

“…Stimulation of a 2B -adrenoceptors in vascular smooth muscle leads to vasoconstriction, which causes the initial hypertension after the administration of a 2 -adrenoceptor agonists [23], and counteracts the hypotensive effects of a 2 -adrenoceptor agonists mediated via the a 2A -subtype. In addition, the a 2B -adrenoceptor seems to be required for the development of salt-induced hypertension [24], and is involved in mediation of the antinociceptive action of nitrous oxide [25,26,27 ] as well as in central thermoregulation [28,29]. The a 2C -adrenoceptor subtype has been demonstrated to modulate dopaminergic neurotransmission, various behavioural responses and to induce hypothermia [30,31].…”

“…This effect of etomidate may contribute to the cardiovascular stability of patients after the induction of anaesthesia with etomidate [34]. The opioid meperidine was shown to be a potent agonist at a 2 -adrenoceptors, and it has been suggested that some actions, especially the antishivering properties, are mediated by this mechanism [28,29].…”

Differential Effects of α2-adrenoceptors in the Modulation of the Thermoregulatory Response in Mice Induced by Meperidine

“…According to our present results, this effect was abolished by administration of the ␣ 2 -adrenoceptor antagonist atipamezole, indicating an involvement of ␣ 2 -adrenoceptors in the mediation of meperidine actions. 10 This conclusion is supported by the fact that meperidine acts as an agonist at ␣ 2 -adrenoceptors in vitro in clinically relevant concentrations, showing highest affinity to the ␣ 2B -adrenoceptor subtype (␣ 2B , 8.6 Ϯ 0.3 M; ␣ 2C , 13.6 Ϯ 1.5 M; ␣ 2A , 38.6 Ϯ 0.7 M).…”

“…Because rodents try to resist hypothermia by nonshivering thermogenesis, we focused on a mouse model of nonshivering thermogenesis that has been used by our group before. 10 These experiments have revealed that meperidine mediates thermoregulatory effects via ␣ 2 -adrenoceptors but did not investigate any ␣ 2 -adrenoceptor subtype specifically. To evaluate the individual role of each of the three ␣ 2 -adrenoceptor subtypes, we compared impact of meperidine using wild-type mice and mice with deletion of the ␣ 2A -, ␣ 2B -, or ␣ 2C -adrenoceptor (knock-out mice).…”

Regulierte Hypothermie nach Herz-Kreislauf-Stillstand

“…Zusammen mit der Beobachtung, dass sich die Wirkung von Pethidin auch durch hohe Dosen Naloxon nur unvollständig unterdrücken lässt [31], legt dies einen Wirkmechanismus unabhän-gig von Opioidrezeptoren nahe. Neuere experimentelle Daten deuten darauf hin, dass die Wirkung vielmehr auf einer agonistischen Wirkung von Pethidin am α 2 -Adrenozeptor beruhen könnte [38]. Die Applikation von Pethidin und dem potenten α 2 -Agonisten Clonidin könnten also 2 Variationen desselben pharmakologischen Prinzips sein.…”