Modulation of opioid analgesia by agmatine

Kolesnikov, Yuri; Jain, Subash; Pasternak, Gavril W.

doi:10.1016/0014-2999(95)00669-9

Cited by 146 publications

(116 citation statements)

References 34 publications

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Section: Discussionmentioning

confidence: 99%

“…Agmatine enhances morphine-induced analgesia in a dose-dependent manner (Kolesnikov et al, 1996;Yesilyurt and Uzbay, 2001;RuizDurantez et al, 2003). Acute administration of low dose of agmatine prevents tolerance following chronic morphine treatment for 10 days (Kolesnikov et al, 1996). Agmatine prevents naloxone-precipitated abstinence syndrome in morphine-dependent rats and attenuates all of the signs of morphine withdrawal syndrome dose-dependently (Aricioglu-Kartal and Uzbay, 1997;Uzbay et al, 2000;Li et al, 2002;Aricioglu et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent evidence supports a neuromodulatroy interaction between agmatine and opioids in which agmatine potentiates some opioid-induced effects. The beneficial potentiating effects of agmatine on morphine analgesia (Kolesnikov et al, 1996;Yesilyurt and Uzbay, 2001;Ruiz-Durantez et al, 2003) are clearly documented. Agmatine has been shown to reduce the development of dependence to morphine (Aricioglu et al, 2004) and attenuates the contractile response to naloxone in morphine-dependent guinea-pig ileum (Aricioglu et al, 2003).…”

Section: Introductionmentioning

confidence: 98%

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Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Tahsili-Fahadan

Yahyavi-Firouz-Abadi

Khoshnoodi

et al. 2005

Neuropsychopharmacol

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The effects of agmatine, an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and its combination with morphine on conditioned place preference (CPP) has been investigated in male mice. Our data show that subcutaneous administration of morphine (1-7.5 mg/kg) significantly increases the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal administration of agmatine (1-40 mg/kg) alone does not induce either CPP or conditioned place aversion, while combination of agmatine and subeffective doses of morphine leads to potent rewarding effects. Lower doses of morphine (0.1, 0.05, and 0.01 mg/kg) are able to induce CPP in mice pretreated with agmatine 1, 5, and 10 mg/kg, respectively. Concomitant intraperitoneal administration of UK 14 304 (0.5 mg/kg), a highly selective a 2 -agonist, with per se noneffective dose of morphine (0.5 mg/kg) and also its combination with noneffective doses of agmatine (1 mg/kg) plus morphine (0.05 mg/kg) produces significant CPP. UK 14 304 (0.05, 0.5 mg/kg) alone, or in combination with agmatine (1, 5 mg/kg) have had no effect. We have further investigated the possible involvement of the a 2 -adrenoceptors in the potentiating effect of agmatine on morphine-induced place preference. Selective a 2 -antagonists, yohimbine (0.005 mg/kg) and RX821002 (0.1, 0.5 mg/kg), block the CPP induced by concomitant administration of agmatine (5 mg/kg) and morphine (0.05 mg/kg). Yohimbine (0.001-0.05 mg/kg) or RX821002 (0.05-0.5 mg/kg) alone or in combination with morphine (0.05 mg/kg) or agmatine (5 mg/kg) fail to show any significant place preference or aversion. Our results indicate that pretreatment of animals with agmatine enhances the rewarding properties of morphine via a mechanism which may involve a 2 -adrenergic receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Tahsili-Fahadan

Yahyavi-Firouz-Abadi

Khoshnoodi

et al. 2005

Neuropsychopharmacol

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“…The kidney is unusual in displaying high constitutive ADC activity, and may be a principal contributor of systemic agmatine (Lortie et al 1996). Agmatine has the capacity to regulate nitric oxide (NO) synthase activity (Galea et al 1996;Abe et al 2000;Satriano et al 2001a) and has been ascribed roles in association with neurotransmitter receptors (Li et al 1994), modulation of opioid analgesia (Kolesnikov et al 1996), and as an ADP-ribose acceptor (Murayama et al 1993). It is structurally analogous to polyamines (putrescine, spermidine and spermine) and can regulate intracellular polyamine content (Satriano et al 1998).…”

mentioning

confidence: 99%

Agmatine Suppresses Mesangial Cell Proliferation by Modulating Polyamine Metabolism

Eto

Isome

Sano

et al. 2006

Tohoku J. Exp. Med.

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Polyamines play an essential role in the growth and differentiation of mammalian cells. The depletion of intracellular polyamines results in the suppression of growth. Proliferation of glomerular mesangial cells (MC) is the most common pathologic change in many forms of glomerulonephritis. Agmatine is a metabolite of arginine via arginine decarboxylase (ADC), highly expressed in the kidney, and unique in its capacity to suppress intracellular polyamine levels required for proliferation. As agmatine enters mammalian cells via the polyamine transport system, its antiproliferative effects may preferentially target cells with increased proliferative kinetics. In the present study, we evaluated the antiproliferative effects of agmatine on human MC in vitro. MC proliferation was stimulated with 20% fetal bovine serum (FBS) or platelet-derived growth factor (PDGF-BB, 20 ng/ml). Cell proliferation was measured using the (4.3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT) proliferation assay. Intracellular polyamine levels were assayed by high performance liquid chromatography, and cell death was assessed by cellular DNA fragmentation enzyme-linked immunosorbent assay. The MTT proliferation assay showed that agmatine significantly suppressed proliferation of human MC treated with 20% FBS or 5% FBS + PDGF as compared to human MC treated with 5% FBS. Polyamine levels were markedly lower in cells treated with agmatine, and proliferation was rescued by administration of putrescine. The fragmented DNA was hardly detected in agmatine-treated human MC. In summary, human MC stimulated to increase their proliferative kinetics are significantly more sensitive to the antiproliferative effects of agmatine than normally cultured cells. Suppressed proliferation of the agmatine-treated human MC is not due to increased cell death. These results suggest that agmatine is a promising drug candidate for the treatment of human mesangial proliferative glomerulonephritis.

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“…Agmatine is widely distributed in the central nervous system, and has various biological actions [21,22] including activating imidazoline receptors, blocking NMDARs, and inhibiting nitric oxide synthase activity [21]. In the past decade, a growing body of evidence from our laboratory and others has shown that systemic administration of agmatine enhances opioid analgesia but attenuates opioid-induced tolerance and addiction [23][24][25][26][27]. Moreover, agmatine modulates the adaptation of glutamate transmission in the nucleus accumbens in chronic morphine-treated rats [28].…”

Section: Introductionmentioning

confidence: 99%

Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats

Wang¹,

Zhao

et al. 2016

Neurosci. Bull.

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Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was downregulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

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Modulation of opioid analgesia by agmatine

Cited by 146 publications

References 34 publications

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Agmatine Suppresses Mesangial Cell Proliferation by Modulating Polyamine Metabolism

Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats

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