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)

Analgesics such as morphine are toxic drugs that kill by producing respiratory depression. Further morphine-like drugs produce a high level of physical dependence and are highly reinforcing in some subjects. A systematic search, conducted over the last 50 years, for safer and less addicting analgesic has revealed that opioid analgesics act on different types of opioid receptors (mu, kappa, and sigma), and that they may function as mixed agonist-antagonists or as partial agonists. Thus some mixed agonists function as competitive antagonists at the mu receptor and as partial or strong agonists at the kappa or sigma receptor. When mixed agonists produce the same pharmacologic effects (eg, analgesia) by acting on different receptors, they invoke the principle of receptor dualisms. Drugs that produce agonist (analgesic) effects by acting on the kappa receptors are an order of magnitude safer than the mu agonists and produce a lesser degree of physical dependence than strong mu agonists. Thus safer, less addicting analgesics have been produced that act either as agonist-antagonists or by being partial agonists.
 ...
PMID:Clinical evidence for different narcotic receptors and relevance for the clinician. 301 58

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

In mice, activation of sigma1 receptors antagonizes opioid analgesia. Sigma antagonists potentiate opioid analgesia, implying that the anti-opioid sigma system is tonically active. Co-administration of haloperidol with the mu opioid morphine, the kappa 1 analgesic U50,488H or the kappa 3 agonist naloxone benzoylhydrazone enhances the analgesic activity of all agents. The effect results from sigma receptor blockade since (-)sulpiride, a selective D2 antagonist which does not block sigma receptors, is inactive.
 ...
PMID:Sigma antagonists potentiate opioid analgesia in rats. 764 23

Patient controlled analgesia (PCA) by intravenous pentazocine was performed to determine its efficacy and the dose required for the pain relief after gynecological or obstetric operations. After obtaining informed consent, studies were performed on 28 female patients (ASA I, II: Mean age 38.1 years: Mean weight, 53.8 kg) who had received gynecological or obstetric operations with lower abdominal incision. Anesthesia given was nitrous oxide and isoflurane combined with epidural anesthesia with 1% mepivacaine used only during the operation. Six patients had cesarian section under spinal anesthesia. No patients received opioid during anesthesia. PCA was performed with a Graseby PCA pump. Lockout time was 8 minutes and the bolus dose was 3 mg. In all the patients, satisfactory pain relief was obtained and no other analgesic was necessary. Mean initial dose was 169.4 micrograms.kg-1 and the mean doses used for following each 6 hours until 24 hours were 409.7, 368.6, 279.3 and 211.1 micrograms.kg-1 respectively. Evaluation of PCA by the patients after the procedure showed excellent (13 patients) good (12) and passable (3) analgesia. No significant complication was observed except temporary nausea in two patients. Satisfactory postoperative pain relief could be obtained by relatively small doses of pentazocine and adverse reactions related especially to sigma receptor could be avoided.
 ...
PMID:[Postoperative pain relief by patient controlled analgesia using intravenous pentazocine]. 773 93

Both (+)-pentazocine and (-)-pentazocine antagonize morphine analgesia equally well. This lack of stereospecificity implies an non-opioid mechanism of action. The antagonism of morphine analgesia by (+)-pentazocine is reversed by haloperidol, a potent dopamine D2 and sigma receptor antagonist. The inactivity of the highly selective dopamine D2 receptor antagonist (-)-sulpiride indicates that both (+)-pentazocine and haloperidol are acting through sigma receptors. Haloperidol, but not (-)-sulpiride, also enhances morphine analgesia. Together, these results suggest the presence of a tonically active anti-opioid sigma system within the brain.
 ...
PMID:Functional antagonism of morphine analgesia by (+)-pentazocine: evidence for an anti-opioid sigma 1 system. 811 6

A cDNA clone (S2-1a) isolated from a mouse brain cDNA library, using a guinea pig sigma1 cDNA as probe, has high homology to the predicted protein sequence of the guinea pig (88%) and human (90%) sigma1 receptors. Northern analysis revealed a major mRNA of approximately 1.8 kb in a wide range of mouse tissues, with highest levels in brain, liver, kidney, and thymus. Southern analysis and chromosomal mapping in the mouse suggested a single-copy gene in region A5-B2 of chromosome 4. Expression of the clone in MCF-7 and CHO cells led to a pronounced increase in (+)-[3H]pentazocine binding with a selectivity profile consistent with sigma1 receptors. In vitro translation yielded a protein of approximately 28 kDa, as did transfection of a probe containing the hemagglutinin (HA) epitope (S2-1a.HA) into CHO cells, as determined by western analysis using an antibody directed against HA. (+)-[3H]-Pentazocine binding to immunopurified HA-tagged receptor demonstrated conclusively that S2-1a.HA encodes a high-affinity (+)-[3H]pentazocine binding site with characteristics of a murine sigma1 receptor. An antisense oligodeoxynucleotide designed from S2-1a potentiated opioid analgesia in vivo.
 ...
PMID:Cloning and characterization of a mouse sigma1 receptor. 960 92

Psychological stress is believed to be implicated in the etiology of affective disorders such as anxiety and depression. To date, a wide range of behavioral responses including analgesia and motor suppression induced by various physiological stressors such as footshock, forced swimming and immobilization have been investigated in animals. However, there is little information concerning behavioral changes in psychological stress. This article describes the experimental procedures and the characteristics of motor suppression in psychological stress, defined as conditioned fear stress (CFS). Mice exhibit a marked suppression of motility when they are re-placed in the same environment in which they had previously received an electric footshock. This motor suppression is regarded as a conditioned emotional response to the environment associated with previous footshock. The motor suppression in CFS is attenuated by sigma receptor agonists such as (+)-N-allylnormetazocine and dextromethorphan, whereas typical anxiolytics (diazepam and chlordiazepoxide) and antidepressants (imipramine and fluoxetine) have no effect. These findings suggest that the CFS model may be useful for investigating the pathogenesis of affective disorders, particularly those considered to be treatment resistant, and for developing their novel therapeutic drugs.
 ...
PMID:[The psychological stress model using motor suppression]. 1020 85

Dopamine systems are intimately involved with opioid actions. Pharmacological studies suggest an important modulatory effect of dopamine and its receptors on opioid analgesia. We have now examined these interactions in a knock-out model in which the dopamine(2) (D(2)) receptor has been disrupted. Loss of D(2) receptors enhances, in a dose-dependent manner, the analgesic actions of the mu analgesic morphine, the kappa(1) agonist U50,488H and the kappa(3) analgesic naloxone benzoylhydrazone. The responses to the delta opioid analgesic [d-Pen(2),d-Pen(5)]enkephalin were unaffected in the knock-out animals. Loss of D(2) receptors also potentiated spinal orphanin FQ/nociceptin analgesia. Antisense studies using a probe targeting the D(2) receptor revealed results similar to those observed in the knock-out model. The modulatory actions of D(2) receptors were independent of final sigma receptor systems because the final sigma agonist (+)-pentazocine lowered opioid analgesia in all mice, including the D(2) knock-out group. Thus, dopamine D(2) receptors represent an additional, significant modulatory system that inhibits analgesic responses to mu and kappa opioids.
 ...
PMID:Potentiation of opioid analgesia in dopamine2 receptor knock-out mice: evidence for a tonically active anti-opioid system. 1156 69

Opioid analgesia is influenced by many factors, including the sigma1 receptor system. Current studies show the importance of supraspinal mechanisms in these sigma1actions. Given supraspinally, the sigma1receptor agonist (+)pentazocine diminished systemic mu, delta, kappa1, and kappa3 opioid analgesia in CD-1 mice. There was a trend for the kappa drugs to be more sensitive to the fixed dose of (+)pentazocine, although the differences did not achieve statistical significance. In contrast to its actions supraspinally, (+)pentazocine was without effect against morphine when both were given spinally. These findings are consistent with a supraspinal site of anti-opioid action of (+)pentazocine. Down-regulating supraspinal sigma1binding sites using an antisense approach potentiated mu, delta, kappa1, and kappa3 analgesia in CD-1 mice. Although equally responsive to mu drugs, BALB-c mice are far less sensitive to kappa analgesics than CD-1 mice. Earlier studies reported that these different responses to kappa drugs between CD-1 and BALB-c were eliminated by the concurrent administration of haloperidol, a sigma1 antagonist. Antisense treatment of BALB-c mice markedly enhanced the response to kappa drugs, as well as morphine. This enhanced response following antisense treatment was similar to that seen with haloperidol. These observations confirm the importance of sigma1 receptors as a modulatory system influencing the analgesic activity of opioid drugs.
 ...
PMID:Sigma1 receptor modulation of opioid analgesia in the mouse. 1186 17

Sigma (sigma) sites are a type of nonopiate receptor whose role has been associated with several behaviours, including anxiety, depression, analgesia, learning processes and psychosis. Although there are several known sigma receptor types, only the type I receptor (sigma 1) has been cloned. To uncover the in vivo relevance of sigma-receptors, we have generated knockout mice for sigma 1. Despite the broad expression pattern found for the sigma 1-gene, homozygous mutant mice are viable, fertile and do not display any overt phenotype, compared with their wild-type litter-mates, in mixed genetic backgrounds. However, a significant decrease in the hypermotility response has been measured in knockout mice upon challenge with (+)SKF-10 047, in agreement with the involvement of sigma 1-receptors in the induction of psychostimulant actions. The activity of sigma 2-receptors seems to be unaffected in sigma 1-mutant mice. These knockout mice could contribute to better understand the in vivo role of sigma-receptors.
 ...
PMID:Generation and phenotypic analysis of sigma receptor type I (sigma 1) knockout mice. 1462 79


1 2 Next >>