1998
DOI: 10.1038/sj.bjp.0702031
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Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I2‐imidazoline ligands

Abstract: 1 Agmatine, the proposed endogenous ligand for imidazoline receptors, has been shown to attenuate tolerance to morphine-induced antinociception (Kolesnikov et al., 1996). The main aim of this study was to assess if idazoxan, an a 2 -adrenoceptor antagonist that also interacts with imidazoline receptors, could also modulate opioid tolerance in rats and to establish which type of imidazoline receptors (or other receptors) are involved. 2 Antinociceptive responses to opioid drugs were determined by the tail-¯ick … Show more

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Cited by 88 publications
(84 citation statements)
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“…This study also demonstrated that the opioid modulation of NF-L proteins also occurs in the prefrontal cortex, a brain region that is also a target for the chronic effects of opioid drugs in humans (Escribá et al, 1994;Busquets et al, 1995;Simonato, 1996). Recently, chronic treatment of rats with morphine also induced a marked decrease (49%) in NF-L immunoreactivity in the frontal cortex (Boronat et al, 1998).…”
mentioning
confidence: 75%
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“…This study also demonstrated that the opioid modulation of NF-L proteins also occurs in the prefrontal cortex, a brain region that is also a target for the chronic effects of opioid drugs in humans (Escribá et al, 1994;Busquets et al, 1995;Simonato, 1996). Recently, chronic treatment of rats with morphine also induced a marked decrease (49%) in NF-L immunoreactivity in the frontal cortex (Boronat et al, 1998).…”
mentioning
confidence: 75%
“…Acute morphine treatment in rats has been shown not to alter the density of nonphosphorylated NF proteins in the VTA (Beitner-Johnson et al, 1992) or to modestly increase their abundance in the frontal cortex (unpublished experiments). In contrast, chronic morphine treatment was associated with marked decreases in nonphosphorylated NF-L (49%) (Boronat et al, 1998) and NF-H (38%) (unpublished experiments) in the rat frontal cortex. It, therefore, appears that the decreases in total immunodensity of NF proteins in brains of opioid addicts are the result of a chronic opioid effect.…”
Section: Discussionmentioning
confidence: 98%
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“…Subsequent development of the idazoxan molecule showed that bulky substitutions at the 2-position of the benzodioxanyl ring gave improved potency and selectivity at the á 2 -receptor. Two molecules showed particularly good characteristics: 2-ethoxy-idazoxan (2-(2-ethoxy-2,3-dihydrobenzo [1,4]dioxin-2-yl)-4,5-dihydro-1H-imidazole, RX 811059) and 2-methoxy-idazoxan (RX 821002, 2-(2-methoxy-2,3-dihydro-benzo [1,4]dioxin-2-yl)-4,5-dihydro-1H-imidazole, Fig. 1) gave improved potency at á 2 -adrenoceptors and á 2 /á 1 selectivity ratios of > 100 (103,114).…”
Section: Introductionmentioning
confidence: 99%
“…IBS ligands were reported to modulate antinociception [121,122], tolerance [123][124][125], and dependence [126][127][128] induced by opioids. In a preliminary study [129], fentanyl (58) and the guanidine moiety, which mimics an endogenous I 2 -IBS ligand agmatine (59) [130], were chosen as the opioid and I 2 -IBS pharmacophores, respectively, to provide twin drugs 61 and 62.…”
Section: Opioid and Imidazoline Binding Site Pharmacophoresmentioning
confidence: 99%