Novel semisynthetic analogs of salvinorin A, a full agonist having extraordinary affinity as well as selectivity for the κ-opioid receptor (KOR), were obtained in good yields. The derivatives are remarkable for their unusual and unique hemiacetal structure in the salvinorin series of compounds. The formation of the hemiacetal occurs with epimerization at C-12, thus preserving the original confi...

Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we ...

Certain behavioral features of buprenorphine, including a bell-shaped curve for antinociception and attenuation of alcohol consumption, are thought to be mediated by activation of nociceptin/orphanin FQ peptide (NOP) receptors, despite moderate affinity and low efficacy at NOP receptors. We hypothesized that ligands with buprenorphine's physical properties, but possessing increased NOP receptor...

Endogenous and exogenous opioids modulate reproductive functions in target cells via opioid receptors (μ, δ, and κ). Sperm motility is a metric of gamete functionality, and serves as a suitable parameter for in vitro drug-induced toxicity assays. This study identifies the presence and location of opioid receptors in pig spermatozoa as well as their functional response after in vitro challenge w...

Opioids are powerful analgesics, but also carry significant side effects and abuse potential. Here we describe a modulator of the μ-opioid receptor (MOR1), the transient receptor potential channel subfamily vanilloid member 1 (TRPV1). We show that TRPV1 binds MOR1 and blocks opioid-dependent phosphorylation of MOR1 while leaving G protein signaling intact. Phosphorylation of MOR1 initiates recr...

The effects of opioids on cigarette smoke-induced plasma exudation were investigated in vivo in the main bronchi of anesthetized guinea pigs, with Evans blue dye as a plasma marker. Acute inhalation of cigarette smoke increased plasma exudation by 216% above air control values. Morphine, 0.1-10 mg/kg but not 30 mg/kg, inhibited the exudation but had no significant effect on substance P-induced ...

Context The therapeutic action of opioid analgesics is compromised by peripheral adverse effects, among which constipation is the most disabling, as laxatives often fail to provide satisfactory relief. To address this problem, opioid receptor antagonists with limited systemic bioavailability (retarded naloxone) or a peripherally restricted site of action (alvimopan, methylnaltrexone) have been ...

BACKGROUND An opioid peptide neuron/humoral feedback regulation might be involved in changes of intraocular pressure (IOP). The aims of this study are to investigate the effects of arcuate nucleus (ARC) and opioid peptides on intraocular pressure (IOP). METHODS Fifty-four healthy purebred New Zealand white rabbits (108 eyes) were randomly divided into 4 groups, including control group, electr...