High-affinity binding of β-carbolines to imidazoline I2B receptors and MAO-A in rat tissues: Norharman blocks the effect of morphine withdrawal on DOPA/noradrenaline synthesis in the brain

Miralles, Antonio; Esteban, Susana; Sastre-Coll, A; Moranta, David; Asensio, Víctor J.; Garcı́a-Sevilla, Jesús A.

doi:10.1016/j.ejphar.2005.06.023

Cited by 72 publications

(49 citation statements)

References 38 publications

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“…three times daily during 5 days with increasing doses of the opiate (10-100 mg/kg) (Boronat et al, 2001) and killed 2 h after the last dose. After this chronic treatment, naloxone (2 mg/kg, i.p., 2 h)-precipitated withdrawal or spontaneous (24 and 48 h) opiate withdrawal was induced, which resulted in the standard behavioral reaction (data not shown; see Gabilondo and García-Sevilla, 1995;Miralles et al, 2005). In another series of chronic experiments, groups of rats were treated with SNC-80 (10 mg/kg) or (À)-U50488H (10 mg/kg) once daily during 5 days.…”

Section: Drug Treatment Of Ratsmentioning

confidence: 97%

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

García-Fuster

Miralles

Garcı́a-Sevilla

2006

Neuropsychopharmacol

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This study was designed to assess the effects of opiate treatment on the expression of Fas-associated protein with death domain (FADD) in the rat brain. FADD is involved in the transmission of Fas-death signals that have been suggested to contribute to the development of opiate tolerance and addiction. Acute treatments with high doses of sufentanil and morphine (m-agonists), , and U50488H (k-agonist) induced significant decreases (30-60%) in FADD immunodensity in the cerebral cortex, through specific opioid receptor mechanisms (effects antagonized by naloxone, naltrindole, or nor-binaltorphimine). The cannabinoid CB 1 receptor agonist WIN 55,212-2 did not alter FADD content in the brain. Chronic (5 days) morphine (10-100 mg/kg), SNC-80 (10 mg/kg), or U50488H (10 mg/kg) was associated with the induction of tachyphylaxis to the acute effects. In morphine-and SNC-80-tolerant rats, antagonistprecipitated (2 h) or spontaneous withdrawal (24-48 h) induced a new and sustained inhibition of FADD (13-50%). None of these treatments altered the densities of caspases 8/3 (including the active cleaved forms) in the brain. Pretreatment of rats with SL 327 (a selective MEK1/2 inhibitor that blocks ERK activation) fully prevented the reduction of FADD content induced by SNC-80 in the cerebral cortex (43%) and corpus striatum (29%), demonstrating the direct involvement of ERK1/2 signaling in the regulation of FADD by the opiate agonist. The results indicate that m-and d-opioid receptors have a prominent role in the modulation of FADD (opposite to that of Fas) shortly after initiating treatment. Opiate drugs (and specifically the d-agonists) could promote survival signals in the brain through inhibition of FADD, which in turn is dependent on the activation of the antiapoptotic ERK1/2 signaling pathway.

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Section: Drug Treatment Of Ratsmentioning

confidence: 97%

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

García-Fuster

Miralles

Garcı́a-Sevilla

2006

Neuropsychopharmacol

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“…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%

Twin and Triplet Drugs in Opioid Research

Fujii

2010

Topics in Current Chemistry

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Twin and triplet drugs are defined as compounds that contain respectively two and three pharmacophore components exerting pharmacological effects in a molecule. The twin drug bearing the same pharmacophores is a "symmetrical twin drug", whereas that possessing different pharmacophores is a "nonsymmetrical twin drug." In general, the symmetrical twin drug is expected to produce more potent and/or selective pharmacological effects, whereas the nonsymmetrical twin drug is anticipated to show both pharmacological activities stemming from the individual pharmacophores (dual action). On the other hand, nonsymmetrical triplet drugs, which have two of the same pharmacophores and one different moiety, are expected to elicit both increased pharmacological action and dual action. The two identical portions could bind the same receptor sites simultaneously while the third portion could bind a different receptor site or enzyme. This review will mainly focus on the twin and triplet drugs with an evaluation of their in vivo pharmacological effects, and will also include a description of their pharmacology and synthesis.

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“…These compounds also have been shown to exert multiple pharmacological effects, including antitumor effects [16], psychoactive effects [17], antiviral effects [18], antimicrobial effects [19], and antiprotozoal effects [20].…”

Section: Introductionmentioning

confidence: 99%

C5 induces different cell death pathways in promastigotes of Leishmania amazonensis

Mendes

Desoti

Silva

et al. 2016

Chemico-Biological Interactions

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Leishmaniasis is a neglected infection that is caused by Leishmania protozoa, affecting millions of people worldwide, mainly in tropical and subtropical regions. This disease has different clinical forms: cutaneous, mucocutaneous, and visceral. The drugs that are currently available for the treatment of this infection have limitations, such as high toxicity, long-term treatment, and leads to drug-resistant strains. Numerous studies, in various experimental models, have sought to develop more effective and less toxic chemotherapeutic agents against leishmaniasis. In the present study, we evaluated the mechanism of cell death that is induced by n-benzyl 1-(4-methoxy)phenyl-9H-β-carboline-3-carboxamide (C5) against Leishmania amazonensis. C5 increased reactive oxygen species production, depolarization of the mitochondrial membrane, DNA fragmentation, decrease of cell volume, lipoperoxidation, the accumulation of lipid bodies, and acidic vesicular organelles (AVOs) and caused the intense formation of autophagic compartments in L. amazonensis promastigotes. The results indicate that C5 causes L. amazonensis death through different pathways.

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High-affinity binding of β-carbolines to imidazoline I2B receptors and MAO-A in rat tissues: Norharman blocks the effect of morphine withdrawal on DOPA/noradrenaline synthesis in the brain

Cited by 72 publications

References 38 publications

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

Twin and Triplet Drugs in Opioid Research

C5 induces different cell death pathways in promastigotes of Leishmania amazonensis

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