The involvement of α2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice

Determination of Adrenergic and Imidazoline Receptor Involvement in Augmentation of Morphine and Oxycodone Analgesia by Clonidine and BMS182874

“…It has also been reported that an opioid antagonist altered adrenergic agonist potency, and an adrenergic antagonist altered opioid agonist potency [45] . The findings of the present study support previously reported results that clonidine potentiates morphine analgesia [9,43,[46][47][48] . However, this is the first report to our knowledge showing that clonidine can also potentiate oxycodone analgesia.…”

“…Clonidine is known to have potent analgesic and sedative effects in rodents. Although clonidine does not discriminate between the three ␣ 2 -adrenergic receptor subtypes, studies on knockout mice have revealed that its sedative and analgesic effects are mainly mediated by the ␣ 2a -adrenergic receptor subtype [41][42][43] . Involvement of ␣ 2 -adrenergic receptors in antinocicep- tive activity was shown in rats treated with clonidine and/ or quercetin, which could be blocked by yohimbine pretreatment [44] .…”

Lewis and Fischer 344 strain differences in α2-adrenoceptors and tyrosine hydroxylase expression

“…Thus, in the field of nociception, the differential contribution of each one of the a 2 -adrenoceptor subtypes to the antinociceptive effect of their ligands remains to be clearly established. There is substantial evidence to think that a 2A -and a 2C -adrenoceptors play a major role in induction of antinociception (Stone et al, 1997;Li and Eisencah, 2001;Kingery et al, 2002;Leiphart et al, 2003;Ozdogan et al, 2004), however the contribution of a 2B -adrenoceptors is poorly understood (Millan, 2002). The specific differences in the a 2B -adrenoceptor expression levels in hypothalamus and hippocampus of F344 and Lewis rats lead us to hypothesize the possible involvement of a 2B -adrenoceptor in pain transmission processes since both areas are involved in the descending control of pain transmission (Millan, 2002), and F344 and Lewis rats exhibit different sensitivity to clonidine analgesia (Herradon et al, 2003a).…”

Clonidina associada à morfina e midazolam em crianças submetidas à ventilação mecânica: estudo aleatório, duplamente encoberto e placebo controlado

“…A ineficácia apresentada pela clonidina, por via enteral, neste estudo, em potencializar os efeitos sedativos em crianças submetidas à VM, poderia ser atribuída a: a) Não efetividade do fármaco: vários estudos já demonstraram a eficácia da clonidina, tanto como sedativos 2,4,7, 18,20,[21][22][23][24][25][26][27][28] , como no tratamento da abstinência 2-4,5,9, 12,16,17,19,29 . Em alguns estudos, quando utilizada para sedação leve, a clonidina teve resultados comparáveis ao fentanil, evitando doses extras de sedativos 21 .…”

“…Porém deve-se ressaltar que neste estudo, as doses de clonidina foram baixas (0,625 e 1,25 µg/kg), quando comparadas às doses preconizadas na literatura. Portanto, quando o objetivo é sedação leve a moderada, a quase totalidade de estudos prévios tem demonstrado que a clonidina tem ação eficaz; b) Doses inadequadas: na maioria dos estudos as doses de clonidina utilizadas variaram de 2 a 6 µg/kg/ dose 5,7,28,30 , sendo que administração de 2 a 3 µg/kg/ dose tem menor efetividade 28 quando comparada a doses maiores de 4 a 6 µg/kg/dose 5,7,30 . Portanto, a dose utilizada neste estudo (5 µg/kg a cada 8h) segue as recomendações, devendo ser consideradas como adequada e efetiva; c) Via de administração inadequada: a maior parte dos estudos emprega a clonidina por via oral, havendo também relatos da utilização por via venosa, seja em doses intermitentes ou em infusão contínua 18,19 .…”