Previous studies have indicated that P-glycoprotein (P-gp) attenuates the central nervous system penetration and central activity of some opioids. The impact of P-gp-mediated efflux on the disposition and efficacy of the synthetic opioid alfentanil currently is unknown. In this study, P-gp-competent [mdr1a(+/+)] and P-gp-deficient [mdr1a(-/-)] mice were used to investigate the impact of P-gp-me...

Data from rodent antinociception models indicate that N-methyl-D-aspartate (NMDA) receptor antagonists do not produce antinociception alone or potentiate morphine antinociception, but do attenuate the development of morphine tolerance. This study examined the antinociceptive effects of the noncompetitive NMDA receptor antagonist dizocilpine, the competitive NMDA receptor antagonist (-)-6-phosph...

Introduction: Previous studies have shown that stimulation of lateral hypothalamus (LH) produces antinociception. Orexin-A (OXA) receptor is strongly expressed in the nucleus locus coeruleus (LC) and orexinergic fibers densely project from LH to LC. In this study, we assessed the role of LC and its OXA receptors in antinociceptive response induced by LH chemical stimulation in the rat. Methods:...

Synthetic cannabinoids (SCs) are an emerging class of abused drugs that differ from each other and the phytocannabinoid ∆9-tetrahydrocannabinol (THC) in their safety and cannabinoid-1 receptor (CB1R) pharmacology. As efficacy represents a critical parameter to understanding drug action, the present study investigated this metric by assessing in vivo and in vitro actions of THC, two well-charact...

The mechanism of the analgesic action of one of the world's most widely used drugs-acetaminophen (paracetamol)-remains largely unknown more than 100 years after its original synthesis. Based on the present findings, this elusiveness appears to have resulted from experimental strategies that concentrated on a single target site or mechanism. Here we report on the use of analyses that we previous...

Antagonistic properties of buprenorphine for and -opioid receptors were characterized in -endorphinand [D-Ala,NMe-Phe,Gly-ol]-enkephalin (DAMGO)-induced antinociception, respectively, with the tail-flick test in male ICR mice. -Opioid receptor agonist -endorphin (0.1–1 g), -opioid receptor agonist DAMGO (0.5–20 ng), or buprenorphine (0.1–20 g) administered i.c.v. dose dependently produced antin...

Gossypin is a bioflavonoid isolated from Hibiscus Vitifolus Linn. The antinociception activity of gossypin has been studied in comparison with the standard antinociception agent, morphine, against the experimental model of tonic continuous pain produced by formalin. Formalin (0.1ml of 1% solution) was injected under the plantar surface of right hind paw of mice and the time an animal spent in l...

It is hypothesized that stimulation of neuronal release of endogenous opioid peptide and the subsequent activation of opioid receptors underlie the antinociceptive action of the anesthetic agent nitrous oxide [9, 10]. In addition, this indirectly induced antinociception is mediated by 6opioid receptors [9, 10]. Cahill et al [2] provided further information on the endogenous opioids involved. Ba...

The effects of twice-daily injections of L-arginine or D-arginine (200 mg/kg i.p.) for 4 days on morphine-induced antinociception, brain nitric oxide synthase activity and brain and serum distribution of morphine and brain m-opioid receptors labeled with [H][D-Ala,MePhe,Gly-ol]enkephalin were determined in male Swiss-Webster mice. Chronic treatment with L-arginine, but not D-arginine, decreased...

Introduction: There is a major societal need for analgesics with less tolerance, dependence, and abuse liability. Preclinical rodent studies suggest that bifunctional ligands both mu (MOPr) delta (DOPr) opioid peptide receptor activity may produce analgesia reduced tolerance other side effects. This study explores the structure-activity relationships (SAR) of our previously reported MOPr/DOPr l...