Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphine was found to elevate spinal dorsal horn 5-hydroxyindole acetic acid (5-HIAA) in a dose-dependent manner. These actions also were naloxone-reversible. In marked contrast other mu, delta and kappa opioid receptor agonists did not alter 5-HIAA levels. These studies clearly indicate that descending spinal 5-hydroxytryptamine (5-HT) pathways are not essential for opiate analgesia.
 ...
PMID:In vivo evaluation of mu, delta and kappa opioid receptor agonists on spinal 5-HT metabolism in the rat. 298 32

In three experiments we examined the analgesic potency of kappa opioid receptor agonists in 2- and 16-day-old rats. Ethylketocyclazocine (1-50 mg/kg) produced similar dose- and time-dependent increases in the latency to retract a hind paw from a noxious thermal stimulus in rats of both ages. Bremazocine (0.001-10 mg/kg), a kappa agonist with reported antagonist activity at mu receptors, was also effective in producing analgesia in 2-day-old rats. The dose-effect relationship for bremazocine was nonmonotonic. Bremazocine analgesia (0.1 mg/kg) was reversed by both naltrexone and MR2266, a putative kappa opioid antagonist. These results are discussed in terms of the functional integrity of a kappa analgesic system in the developing rat.
 ...
PMID:Ethylketocyclazocine and bremazocine analgesia in neonatal rats. 306 43

The analgesia produced by combinations of low-dose naloxone with pentazocine or morphine was studied in 105 patients with moderately severe postoperative pain after standardized surgery for removal of impacted third molars. Pain intensity was quantified using a visual-analogue scale. To eliminate the release of endogenous opioids produced by the placebo component of open drug administration, all injections were made by a preprogrammed infusion pump. The analgesia produced by pentazocine, an agonist-antagonist opiate-analgesic acting predominantly at the kappa opiate receptor, was potentiated by low-dose naloxone, whereas the analgesia produced by morphine, a mu-agonist, was attenuated by low-dose naloxone. To evaluate whether similar potentiation would be present in an animal model, and specifically, in the absence of diazepam, which patients receive, we performed an analogous experiment in rats in which nociceptive threshold was determined using the Randall-Selitto paw-withdrawal test. The results were completely analogous to the clinical results: pentazocine analgesia was potentiated by low-dose naloxone, whereas morphine analgesia was attenuated by low-dose naloxone. These data demonstrate a novel interaction between opiates, and suggest a rationale for opiate combinations to produce potent analgesia with fewer autonomic side effects and less abuse potential than presently available analgesics.
 ...
PMID:Potentiation of pentazocine analgesia by low-dose naloxone. 318 54

Three opioid agonists ([D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and U50488H) were tested independently for their ability to produce analgesia in the formalin test. These agonists were chosen based upon their ability to act selectively at mu, delta and kappa opioid receptor types respectively. Rats received one intracerebroventricular (i.c.v.) injection of an agonist 20 min after subcutaneous injection of 15% formalin into a rear paw. Formalin injection produces continuous pain that results in two stereotypic behaviors, paw licking and paw lifting. Ten minutes after i.c.v. injection rats were observed for an 8 min period and scored for formalin-induced behavior. All agonists produced analgesia as indicated by a dose-dependent attenuation of formalin-induced behavior. At the doses tested, the rank order of analgesic efficacy was DAGO greater than DPDPE greater than U50488H. We suggest that centrally located mu, delta and kappa opioid receptors can each modulate the perception of this clinically relevant form of continuous pain. Additionally, the highest dose of DPDPE tested significantly increased rearing whereas DAGO and U50488H failed to affect rearing.
 ...
PMID:Analgesia produced by centrally administered DAGO, DPDPE and U50488H in the formalin test. 321 76

U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide) displays analgesic actions in a variety (thermal, pressure and irritant) of assays in mice and rats. Naloxone and MR-2266 block this analgesic effect; thus it is mediated by opioid receptors. However, when compared to morphine analgesia, the naloxone and MR-2266 pA2 values for U-50,488 analgesia were much lower and higher, respectively. Likewise, although tolerance occurs to both morphine and U-50,488 analgesia, there was no cross-tolerance between these drugs, and U-50,488 does not cause morphine-type physical dependence. These observations suggest that different opioid receptors mediate the analgesic effects of morphine and U-50,488. The effects of U-50,488 appear to be mediated by the so-called kappa opioid receptor. In contrast to U-50,488, other reputed kappa opioid agonists displayed varying degrees of mu agonist (ketazocine and ethylketocyclazocine) and narcotic antagonist (bremazocine) activities. Thus U-50,488 is a more selective kappa agonist. This conclusion is further supported by binding studies; of all compounds tested, U-59,488 displacement of [3H]ethylketocyclazocine binding was uniquely not blocked by high concentrations of dihydromorphine. In addition to analgesia, this selective kappa agonist also causes opioid receptor-mediated sedation, diuresis and corticosteroid elevations. U-50,488 is a useful tool for studying contrasting kappa and mu opioid receptor-mediated effects.
 ...
PMID:U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist. 612 21

There is substantial evidence for the role of endogenous opioid peptides in the regulation of appetite. This communication examines the possible opioid peptide mechanism(s) which are involved in appetite regulation. In the rat, activation of both the dynorphin-kappa opioid receptor and the beta-endorphin-epsilon opioid receptor appear to enhance feeding, most probably acting in different areas of the central nervous system. It also appears that rats may have a mu anorectic system. Too few studies have been undertaken to define whether the delta or sigma receptor systems are also involved in feeding responses. It is becoming apparent that a great deal of species diversity exists in the feeding responses to opiates, making it difficult to extrapolate the results obtained in rats to other species. In humans, studies with naloxone suggest an opioid sensitive feeding system which possibly is specifically involved in the regulation of carbohydrate uptake. In addition, we report here preliminary data suggesting the presence of a mu anorectic system in humans. Thus, analogous to the findings for the role of opioid receptors in analgesia, it appears that multiple opioid receptors may be involved in appetite regulation, each receptor relating to a different aspect of feeding.
 ...
PMID:Which opioid receptor mechanism modulates feeding? 614 13

The naturally occurring indole alkaloid ibogaine is of interest because of its reported ability to block drug seeking behavior for extended periods. The compound also potentiates morphine-induced analgesia in mice and reduces certain naltrexone-precipitated withdrawal signs in morphine-dependent rats. Although these results might suggest ibogaine interaction with opioid receptors, previous receptor binding studies (Brain Res. 571:242-247, 1980) found that ibogaine had a Ki value of only 2 microM for the kappa opioid receptor and was virtually inactive in blocking mu and delta receptor binding (Ki > 100 microM). The present investigation of ibogaine interaction with the mu opioid receptor from mouse forebrain labeled with [3H]-naloxone, however, yielded significantly more potent mu opioid Ki values. LIGAND analysis indicated that the data were best fit by a two site binding model, with Ki values of about 130 nM and 4 microM, reflecting ibogaine recognition of different agonist affinity states of the receptor. Inclusion of 100 mM NaCl in the assay to induce the agonist low affinity state of the receptor, reduced ibogaine's inhibition of [3H]-naloxone binding. These results suggest that ibogaine is an agonist at the mu opioid receptor with a Ki value of about 130 nM, potentially explaining ibogaine's antinociceptive effects as well as its reported reduction of opioid withdrawal symptoms and attenuation of drug seeking behavior.
 ...
PMID:High affinity ibogaine binding to a mu opioid agonist site. 747 26

Intrathecal injection of dynorphin A produced dual effects on sensory and motor functions in the spinal cord of the rat. At a dose of 5 nmol, dynorphin A produced an increase in tail flick latency (TFL) as well as a reversible motor paralysis as assessed by change in the angle of inclined plane. At a dose of 10 or 20 nmol, dynorphin produced a motor paralysis lasting for up to 24 hours. The effect of dynorphin A on the sensory function of the spinal cord was shown by an increase in the vocalization threshold induced by electrical stimulation of the tail, at dose range of 1.25-10 nmol, with a quick onset (5 min) and relatively short duration (within 60 min). Unlike tail flick reaction which involves spinal motor function, tail stimulation-induced vocalization threshold is a relatively pure index for spinal nociceptive activities. The differential effect of dynorphin on sensory and motor function was supported by the evidence that (1) dynorphin-induced analgesic effect (increase in vocalization threshold) was naloxone reversible, whereas dynorphin-induced motor paralysis was naloxone resistant. (2) Nor-BNI, a specific antagonist for kappa opioid receptor, blocked the sensory effect of dynorphin, but had no influence on motor effect of dynorphin. It is thus concluded that dynorphin has both analgesic and paralytic effects in spinal cord. The analgesia shown by an increase of vocalization threshold is an opioid effect, most probably mediated by kappa opioid receptor; the paralytic effect, however, is a non-opioid effect. The increase of TFL induced by dynorphin involves both sensory (analgesia) and motor (paralysis) effects.
 ...
PMID:Comparative study of the analgesic and paralytic effects induced by intrathecal dynorphin a in rats. 759 18

It is reported that intrathecal (it) injection of low dose of dynorphin (Dyn) induces no analgesia while high dose of Dyn induces analgesia and might lead to hindlimb paralysis and loss of reflex via NMDA receptor. We hypothesized that NMDA receptor antagonists may reveal kappa analgesic-potential of subliminal dose of Dyn. Twenty-four hours after intrathecal cannulation, tail flick latency was measured before and after it of drugs. Combination of Dyn A- (1-13) 5 nmol or U50488H 100 nmol, a kappa receptor agonist with either DL-2-amino-5-phosphonovaleric acid (5 and 10 nmol) or kynurenic acid (25 and 50 nmol) it induced synergistic analgesia, which was reversed by nor-binaltorphimine 15 nmol, a kappa receptor antagonist. It is concluded that kappa opioid receptor agonists and NMDA receptor antagonists synergistically induce analgesia via interaction with their receptors.
 ...
PMID:[Intrathecal co-administration of kappa opioid receptor agonists and NMDA receptor antagonists induces synergistic analgesia in rats]. 770 39

A novel G protein-coupled receptor was cloned by PCR and homology screening. Its deduced amino acid sequence is 47% identical overall to the mu, delta and kappa opioid receptors and 64% identical in the putative transmembrane domains. When transiently expressed in COS-7 cells this receptor did not bind any of the typical mu, delta or kappa opioid receptor ligands with high affinity. In situ hybridization analysis revealed that LC132 mRNA is highly expressed in several rat brain areas, including the cerebral cortex, thalamus, subfornical organ, habenula, hypothalamus, central gray, dorsal raphe, locus coeruleus and the dorsal horn of the spinal cord. Based on this distribution and its high homology with the mu, delta and kappa opioid receptors, it is proposed that LC132 is a new member of the opioid receptor family that is involved in analgesia and the perception of pain.
 ...
PMID:Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a mu, delta or kappa opioid receptor type. 803 19


<< Previous 1 2 3 4 5 6 7 8 Next >>