Principles: Mechanisms and modeling of synergism in cellular responses

Barrera, Nelson P.; Morales, Bernardo; Torres, Soledad; Villalón, Manuel

doi:10.1016/j.tips.2005.08.003

Cited by 41 publications

(28 citation statements)

References 31 publications

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“…The synergism obtained by coadministration of gabapentin with nortriptyline is consistent with the idea that the concurrent administration requires that the drugs combined have different mechanisms, so that decreasing the dose to avoid toxicity still entails increasing or maintaining the same efficacy [29] and all levels of cell function are involved [30]. According to this, it is likely that the synergistic effect is based on different antinociceptive pathways that are activated by combining these drugs.…”

Section: Discussionsupporting

confidence: 74%

Antinociceptive Synergism of Gabapentin and Nortriptyline in Mice with Partial Sciatic Nerve Ligation

Miranda¹,

Noriega²,

Zepeda

et al. 2015

Pharmacology

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Background and Methods: Neuropathic pain results from nerve injury, and gabapentin, an antiepileptic drug, has been approved for the treatment of several types of neuropathic pain. On the other hand, nortriptyline, an antidepressant drug, has been suggested as an alternative treatment. In partial sciatic nerve ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was evaluated by the hot plate assay using isobolographic analysis. Results: Gabapentin (3-100 mg/kg, i.p.) or nortriptyline (1-30 mg/kg, i.p.) induced dose-dependent antinociception, with an ED₅₀ of 11.60 ± 0.54 mg/kg for gabapentin and of 5.16 ± 0.21 mg/kg for nortriptyline. The potency of gabapentin and nortriptyline in PSNL mice at 7 and 14 days after ligation was significantly increased (p < 0.05). Coadministration of gabapentin with nortriptyline, at a 1:1 ratio of their ED₅₀, had a synergistic effect, with an interaction index of 0.311 and 0.348 for these mice at 7 and 14 days, respectively. Conclusion: The data showed a synergy in antinociception at a gabapentin-to-nortriptyline ratio of 1:1 in PSNL mice. This finding suggests that this combination could provide a therapeutic alternative that can be used for neuropathic pain management.

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Section: Discussionsupporting

confidence: 74%

Antinociceptive Synergism of Gabapentin and Nortriptyline in Mice with Partial Sciatic Nerve Ligation

Miranda¹,

Noriega²,

Zepeda

et al. 2015

Pharmacology

View full text Add to dashboard Cite

show abstract

“…It is well known that synergism, induced by drugs with different mechanisms of action, should depend on several variables, i.e. type and intensity of the stimuli, relative ratio of drug concentration and the location and amplification of the transduction mechanisms [23].…”

Section: Discussionmentioning

confidence: 99%

Synergism Between Fentanyl and Tramadol in Tonic Inflammatory Pain: the Orofacial Formalin Test

et al. 2011

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Opioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.p. administration of tramadol and fentanyl induced a dose-dependent antinociception with an ED(50) of 2.97 ± 0.32 mg/kg for phase I and 1.79 ± 0.30 mg/kg for phase II and 0.062 ± 0.0040 mg/kg in phase I and 0.041 ± 0.0039 mg/kg in phase II, respectively. The coadministration of fentanyl with tramadol induced synergism in both phases of the test with an interaction index of 0.343 and 0.163 for phase I and phase II, respectively. This finding could be explained by the more complex pharmacology of tramadol compared to fentanyl.

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“…Synergistic responses are known to be involved in virtually all levels of cell function: for example, the control of gene transcription; ion channel activity, activation of receptors, deleterious mutations and non-covalent interaction between membrane lipids and proteins (Barrera et al 2005). In addition, it has been postulated that the use of multiple drugs with different mechanisms of action may be the basis of synergism (Chou 2006).…”

Section: Discussionmentioning

confidence: 99%

Synergism between COX-3 inhibitors in two animal models of pain

et al. 2010

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These actions can be related to the differential selectivity of the drugs for inhibition of COX isoforms and also to the several additional antinociception mechanisms and pathways initiated by the analgesic drugs on pain transmission. Since the efficacy of the combination of metamizol with paracetamol has been demonstrated in the present study, this association could have a potential beneficial effect on the pharmacological treatment of clinical pain.

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Principles: Mechanisms and modeling of synergism in cellular responses

Cited by 41 publications

References 31 publications

Antinociceptive Synergism of Gabapentin and Nortriptyline in Mice with Partial Sciatic Nerve Ligation

Antinociceptive Synergism of Gabapentin and Nortriptyline in Mice with Partial Sciatic Nerve Ligation

Synergism Between Fentanyl and Tramadol in Tonic Inflammatory Pain: the Orofacial Formalin Test

Synergism between COX-3 inhibitors in two animal models of pain

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