Summary: An opioid analgesic with actions and uses similar to MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1095)

Top Publications

  1. Johannessen M, FONTANILLA D, Mavlyutov T, Ruoho A, Jackson M. Antagonist action of progesterone at ?-receptors in the modulation of voltage-gated sodium channels. Am J Physiol Cell Physiol. 2011;300:C328-37 pubmed publisher
  2. Johannessen M, Ramachandran S, Riemer L, Ramos Serrano A, Ruoho A, Jackson M. Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems. Am J Physiol Cell Physiol. 2009;296:C1049-57 pubmed publisher
    ..The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity. ..
  3. Tchedre K, Huang R, Dibas A, Krishnamoorthy R, Dillon G, Yorio T. Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction. Invest Ophthalmol Vis Sci. 2008;49:4993-5002 pubmed publisher
    ..Regulation of calcium influx in RGCs by sigma-1 receptor ligands may represent in part the neuroprotective effect of sigma-1 receptors. ..
  4. Wilke R, Mehta R, Lupardus P, Chen Y, Ruoho A, Jackson M. Sigma receptor photolabeling and sigma receptor-mediated modulation of potassium channels in tumor cells. J Biol Chem. 1999;274:18387-92 pubmed
    ..These results demonstrate that ion channels can be modulated by a receptor that does not have seven membrane-spanning domains and does not employ G-proteins. Sigma receptors thus modulate ion channels by a novel transduction mechanism. ..
  5. Culp S, Rominger D, Tam S, De Souza E. [3H]DuP 734 [1-(cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'- oxoethyl)-piperidine HBr]: a receptor binding profile of a high-affinity novel sigma receptor ligand in guinea pig brain. J Pharmacol Exp Ther. 1992;263:1175-87 pubmed
    ..In summary, [3H]DuP 734 is a novel ligand that binds with high affinity to sigma receptors in brain. ..
  6. Matsuno K, Senda T, Kobayashi T, Mita S. Involvement of sigma 1 receptor in (+)-N-allylnormetazocine-stimulated hippocampal cholinergic functions in rats. Brain Res. 1995;690:200-6 pubmed
    ..Such stereoselectivity and antagonism imply an involvement of sigma 1 receptors in these (+)-SKF-10,047-stimulated hippocampal cholinergic functions. ..
  7. Carroll M. Oral self-administration of N-allylnormetazocine (SKF-10,047) stereoisomers in rhesus monkeys: substitution during phencyclidine self-administration and withdrawal. Pharmacol Biochem Behav. 1988;30:493-500 pubmed
    ..Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (+/-)-NANM were reinstated in subsequent replications of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  8. Schindler C, White M, Goldberg S. Effects of morphine, ethylketocyclazocine, N-allylnormetazocine and naloxone on locomotor activity in the rabbit. Psychopharmacology (Berl). 1990;101:172-7 pubmed
  9. Karasawa J, Yamamoto H, Yamamoto T, Sagi N, Horikomi K, Sora I. MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells. Life Sci. 2002;70:1631-42 pubmed
    ..These observations suggest that the MS-377 indirectly modulated the NMDA receptor ion-channel complex, and the anti-psychotic activities of MS-377, in part, are attributable to such on action via sigma-1 receptor. ..

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  1. Gharagozlou P, Demirci H, David Clark J, Lameh J. Activity of opioid ligands in cells expressing cloned mu opioid receptors. BMC Pharmacol. 2003;3:1 pubmed publisher
    ..Furthermore, these results can assist in understanding the physiological effect of many opioid ligands acting through mu opioid receptors. ..
  2. Beaton J, Stemsrud K, Monaghan D. Identification of a novel N-methyl-D-aspartate receptor population in the rat medial thalamus. J Neurochem. 1992;59:754-7 pubmed
  3. Gonzalez Alvear G, Werling L. Regulation of [3H]dopamine release from rat striatal slices by sigma receptor ligands. J Pharmacol Exp Ther. 1994;271:212-9 pubmed
    ..Our findings on the regulation of dopamine support earlier assertions that sigma receptors may be important in the regulation of motor function. ..
  4. Brent P, Haynes H, Jarvie P, Mudge L, Sim A, Dunkley P. Phosphorylation of synapsin I and dynamin in rat forebrain synaptosomes: modulation by sigma (sigma) ligands. Neurosci Lett. 1995;191:71-4 pubmed
  5. Jin J, Yamamoto T, Watanabe S. The involvement of sigma receptors in the choice reaction performance deficits induced by phencyclidine. Eur J Pharmacol. 1997;319:147-52 pubmed
    ..These findings indicated that PCP (3.2 mg/kg) significantly induced attention deficit in a 3-choice serial reaction time task, and that this process may be mediated by sigma receptors. ..
  6. Mamiya T, Noda Y, Noda A, Hiramatsu M, Karasawa K, Kameyama T, et al. Effects of sigma receptor agonists on the impairment of spontaneous alternation behavior and decrease of cyclic GMP level induced by nitric oxide synthase inhibitors in mice. Neuropharmacology. 2000;39:2391-8 pubmed
    ..Further, the ameliorating effects of (+) SKF 10,047 on the impairment of spontaneous alternation behavior may be mediated through activation of guanylate cyclase, but not nitric oxide synthase in the hippocampus of mice. ..
  7. Pascaud X, Defaux J, Roze C, Junien J. Effect of selective sigma ligands on duodenal alkaline secretion in the rat. J Pharmacol Exp Ther. 1990;255:1354-9 pubmed
    ..01). None of the antagonists changed the basal bicarbonate output but vagotomy, which induced a 52% (P less than 0.01) decrease.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  8. Urani A, Romieu P, Roman F, Yamada K, Noda Y, Kamei H, et al. Enhanced antidepressant efficacy of sigma1 receptor agonists in rats after chronic intracerebroventricular infusion of beta-amyloid-(1-40) protein. Eur J Pharmacol. 2004;486:151-61 pubmed
    ..The present study suggests that sigma(1) receptor agonists, due to their enhanced efficacy in a nontransgenic animal model, may alleviate Alzheimer's disease-associated depressive symptoms. ..
  9. Roman F, Pascaud X, Martin B, Vauche D, Junien J. JO 1784, a potent and selective ligand for rat and mouse brain sigma-sites. J Pharm Pharmacol. 1990;42:439-40 pubmed
    ..2 and 3.5 mg kg-1, respectively. The high selectivity of JO 1784 for the sigma-binding site was assessed by its lack of significant affinity for more than 20 other sites including those for phencyclidine. ..
  10. Price G, Ahier R, Middlemiss D, Singh L, Tricklebank M, Wong E. In vivo labelling of the NMDA receptor channel complex by [3H]MK-801. Eur J Pharmacol. 1988;158:279-82 pubmed
    ..1 mg/kg) and (+)-SKF 10,047 (34.5 mg/kg). The potency of these drugs in this in vivo binding assay was highly correlated (r = 0.97) with their functional effects as antagonists of N-methyl-DL-aspartate-induced tonic convulsions. ..
  11. Tabatabai S, Zarrindast M, Lashkari S, Shafiee A. Synthesis, conformational analysis and antinociceptive activity of 1-[N-methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahydroisoquinoline derivatives. Arzneimittelforschung. 1999;49:1001-5 pubmed
    ..Conformational analysis and superimposition of energy minima conformers of the compounds on phenazocine revealed that the main proposed opioid pharmacophores were well matched.
  12. Bouchard P, Roman F, Junien J, Quirion R. Autoradiographic evidence for the modulation of in vivo sigma receptor labeling by neuropeptide Y and calcitonin gene-related peptide in the mouse brain. J Pharmacol Exp Ther. 1996;276:223-30 pubmed
    ..These results extend findings obtained in the hippocampal formation and demonstrate the existence of in vivo modulatory effects of NPY and CGRP-related peptides on sigma sites throughout the mouse brain. ..
  13. Bunn S, Brent P, O Malley S. The sigma compounds 1,3-di-o-tolylguanidine and N-allylnormetazocine inhibit agonist-stimulated inositol phospholipid metabolism in bovine adrenal medullary cells. Neurochem Res. 1994;19:709-12 pubmed
    ..These data demonstrate that sigma-compounds inhibit agonist-stimulated inositol phospholipid metabolism in bovine adrenal medullary cells, with a degree of selectivity towards the muscarinic response. ..
  14. Brown C, Fezoui M, Selig W, Schwartz C, Ellis J. Antitussive activity of sigma-1 receptor agonists in the guinea-pig. Br J Pharmacol. 2004;141:233-40 pubmed
    ..While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated <0.3 mg kg(-1)) suggest that there may be a peripheral component to the antitussive effect. ..
  15. Matsuno K, Matsunaga K, Mita S. Acute effects of sigma ligands on the extracellular DOPAC level in rat frontal cortex and striatum. Neurochem Res. 1995;20:233-8 pubmed
    ..In addition, the effects of benzomorphan sigma ligands on the central DA neurons were different from those of non-benzomorphan sigma ligands. ..
  16. Zhou Q, Carlsson A, Botros M, Fransson R, Sandström A, Gordh T, et al. The C-terminal amidated analogue of the substance P (SP) fragment SP(1-7) attenuates the expression of naloxone-precipitated withdrawal in morphine dependent rats. Peptides. 2009;30:2418-22 pubmed publisher
    ..We conclude that the SP(1-7) amide mimics the effect of the native SP fragment and that the mechanisms for its action involve a sigma receptor site. ..
  17. Balster R. Substitution and antagonism in rats trained to discriminate (+)-N-allylnormetazocine from saline. J Pharmacol Exp Ther. 1989;249:749-56 pubmed
    ..Instead, activity at the PCP receptor is predictive of (+)-NANM-like effects. ..
  18. Beart P, O Shea R, Manallack D. Regulation of sigma-receptors: high- and low-affinity agonist states, GTP shifts, and up-regulation by rimcazole and 1,3-Di(2-tolyl)guanidine. J Neurochem. 1989;53:779-88 pubmed
    ..sigma-Receptors are likely to be linked to a G protein and are functionally involved in the CNS. ..
  19. Tsao L, Su T. IP3 receptor antagonist heparin uncompetitively inhibits [3H](+)-SKF-10047 binding to sigma receptors. Eur J Pharmacol. 1996;311:R1-2 pubmed
    ..These results suggest that sigma receptors may bear some relationship with IP3 receptor associated proteins or channels. ..
  20. Maurice T, Roman F, Su T, Privat A. Beneficial effects of sigma agonists on the age-related learning impairment in the senescence-accelerated mouse (SAM). Brain Res. 1996;733:219-30 pubmed
  21. Palmer C, Mahen R, Schnell E, Djamgoz M, Aydar E. Sigma-1 receptors bind cholesterol and remodel lipid rafts in breast cancer cell lines. Cancer Res. 2007;67:11166-75 pubmed
    ..The findings of this study provide a biological basis for the potential therapeutic applications of lipid raft cholesterol regulation in cancer therapy using sigma receptor drugs. ..
  22. Freeman F, Young I. Involvement of the sigma receptor in passive-avoidance learning in the day-old chick during the second wave of neuronal activity. Neurobiol Learn Mem. 2001;75:346-52 pubmed
    ..It is suggested that the sigma-receptor may exert its effect on passive-avoidance memory consolidation during the later stages of long-term memory formation by modulation of memory-related neurotransmission. ..
  23. Delaunois A, De Ron P, Detrait E, Guyaux M. Inhibitory effects of sigma-1 ligands on handling-induced tachycardia in conscious tethered rats. Fundam Clin Pharmacol. 2013;27:354-63 pubmed publisher
    ..Although additional investigations are needed to fully understand this role, it might offer new therapeutic perspectives to ?1 ligands in the cardiovascular sphere. ..
  24. Glennon R, Young R, Herndon J. Antagonism of a (+)N-allylnormetazocine stimulus by (-)PPAP and several structurally related analogs. Pharmacol Biochem Behav. 1993;45:865-9 pubmed
    ..They do, however, demonstrate that sigma-ligands with little to no affinity for PCP receptors are capable of antagonizing the (+)NANM stimulus. ..
  25. McCann D, Su T. Haloperidol competitively inhibits the binding of (+)-[3H]SKF-10,047 to sigma sites. Eur J Pharmacol. 1990;180:361-4 pubmed
    ..In experiments using membranes from both guinea pig and rat brain the apparent Kd of (+)-[3H]SKF-10,047 for sigma sites was significantly increased, whereas the apparent Bmax was not altered by the addition of 10 nM haloperidol. ..
  26. Iwamoto E. Evidence for a model of activation of central sigma systems. Life Sci. 1989;44:1547-54 pubmed
    ..5 mg/kg of MR2266. The data suggest that the manifestation of the (+)-BUT/(-)-NAN-induced syndrome depends upon intact transmission at central sigma sites. ..
  27. Matsuno K, Senda T, Matsunaga K, Mita S. Ameliorating effects of sigma receptor ligands on the impairment of passive avoidance tasks in mice: involvement in the central acetylcholinergic system. Eur J Pharmacol. 1994;261:43-51 pubmed
    ..In addition, the anti-amnesic effect of (+)-SKF-10,047 was superior to those of other sigma receptor ligands, and was mediated by both the sigma receptor and the central acetylcholinergic system...
  28. Bao W, Zhen F, Sun F, Zhang A. Effects of sigma and phencyclidine receptor ligands on electric field-stimulated rabbit ear artery constriction in vitro. Zhongguo Yao Li Xue Bao. 1994;15:320-2 pubmed
    ..05), and 466 +/- 95 mg (n = 5, P < 0.05), respectively. These results revealed that there were mainly Phe receptors but hardly any sigma receptors in the arteries. ..
  29. Cobos E, Baeyens J, Del Pozo E. Phenytoin differentially modulates the affinity of agonist and antagonist ligands for sigma 1 receptors of guinea pig brain. Synapse. 2005;55:192-5 pubmed
    ..Therefore, determining in vitro the differential modulation by DPH of sigma(1) ligand affinity appears to constitute a procedure that can predict the pharmacological profile of different sigma(1) ligands. ..
  30. Jackson A, Sanger D. Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-D-aspartate receptors?. Psychopharmacology (Berl). 1988;96:87-92 pubmed
    ..These findings are discussed in the light of the hypothesis that the behavioural effects of PCP are mediated via a reduction of neurotransmission at the NMDA-subtype of glutamate receptors. ..
  31. Wang H, Chou Y, Liao J, Chen C. Dimemorfan enhances acetylcholine release from rat hippocampal slices. Brain Res. 2004;1008:113-5 pubmed
    ..3 microM). ..
  32. Tricklebank M, Singh L, Oles R, Preston C, Iversen S. The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. Eur J Pharmacol. 1989;167:127-35 pubmed
    ..For all compounds except CPP, the anticonvulsant ED50 dose was close to the minimum effective dose to induce motor stimulation: CPP was 5- to 10-fold more potent as an anticonvulsant.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  33. Loo P, Braunwalder A, Lehmann J, Williams M, Sills M. Interaction of L-glutamate and magnesium with phencyclidine recognition sites in rat brain: evidence for multiple affinity states of the phencyclidine/N-methyl-D-aspartate receptor complex. Mol Pharmacol. 1987;32:820-30 pubmed
    ..The results of the present study are consistent with the finding that agonists of the NMDA receptor induce a high affinity state of the PCP receptor. ..
  34. Nishikawa H, Hashino A, Kume T, Katsuki H, Kaneko S, Akaike A. Involvement of direct inhibition of NMDA receptors in the effects of sigma-receptor ligands on glutamate neurotoxicity in vitro. Eur J Pharmacol. 2000;404:41-8 pubmed
    ..These results suggested that a direct interaction with NMDA receptors but not with sigma receptors plays a crucial role in the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors. ..
  35. Boyce S, Rupniak N, Steventon M, Cook G, Iversen S. Psychomotor activity and cognitive disruption attributable to NMDA, but not sigma, interactions in primates. Behav Brain Res. 1991;42:115-21 pubmed
    ..These findings indicate that the psychomotor and cognitive effects of PCP-like and sigma ligands in primates are mediated through interactions at NMDA, not sigma, receptors. ..
  36. DeLander G, Wahl J. In vivo characterization of phencyclidine/sigma agonist-mediated inhibition of nociception. Eur J Pharmacol. 1989;159:149-56 pubmed
    ..Our results confirm the existence of NMDA/PCP receptor complexes in spinal systems mediating nociception and suggest agonists may induce antinociception by interacting with spinal PCP receptors.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  37. Vaupel D. Tripelennamine interactions with the psychotomimetic sigma agonist N-allylnormetazocine. Pharmacol Biochem Behav. 1989;33:717-20 pubmed
    ..The findings are inconsistent with the hypothesis that tripelennamine antagonizes the psychotomimetic NANM-like effects of pentazocine to make pentazocine-tripelennamine combinations (T's and Blues) more desirable as a heroin substitute...
  38. Marquis K, Paquette N, Gussio R, Moreton J. Comparative electroencephalographic and behavioral effects of phencyclidine, (+)-SKF-10,047 and MK-801 in rats. J Pharmacol Exp Ther. 1989;251:1104-12 pubmed
    ..The data indicate that subtle differences in the effects of these drugs can be detected using EEG power spectral analysis.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  39. Kushner L, Zukin S, Zukin R. Characterization of opioid, sigma, and phencyclidine receptors in the neuroblastoma-brain hybrid cell line NCB-20. Mol Pharmacol. 1988;34:689-94 pubmed
    ..This site is similar to the rat brain PCP receptor. The NCB-20 cell line is the only cultured cell line that has been demonstrated to have PCP receptors. ..
  40. Tanaka M, Chaki S, Imagawa Y, Okuyama S, Muramatsu M, Otomo S. FH-510, a potent and selective ligand for rat brain sigma recognition sites. Eur J Pharmacol. 1993;238:89-92 pubmed
    ..54 mg/kg, which is 14-fold more potent than that for (+)-alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol ((+)-BMY14802) (7.6 mg/kg). These results suggest that FH-510 may be a potent and selective sigma ligand. ..
  41. Noda Y, Kamei H, Kamei Y, Nagai T, Nishida M, Nabeshima T. Neurosteroids ameliorate conditioned fear stress: an association with sigma receptors. Neuropsychopharmacology. 2000;23:276-84 pubmed
    ..Further, the endogenous DHEAS may be involved in the expression of conditioned fear stress response in mice. ..
  42. Picker M, Dykstra L. Comparison of the discriminative stimulus properties of U50,488 and morphine in pigeons. J Pharmacol Exp Ther. 1987;243:938-45 pubmed
    ..The present findings illustrate further the unique behavioral response of pigeons to the discriminative stimulus properties of the kappa agonists, and establishes that pigeons can discriminate between mu and some kappa agonists. ..
  43. Jerram A, Smith P, Darlington C. The effects of (+)-SKF10047 and ketamine hydrochloride on stereotyped behaviour, locomotor activity and ataxia in guinea pig. Eur J Pharmacol. 1996;307:269-73 pubmed
    ..5 and 25.0 mg/kg, i.p). However, at the lower dose (i.e., 12.5 mg/kg), significant ataxia and a significant impairment of the righting reflex were produced. ..
  44. Kitanaka J, Kitanaka N, Tatsuta T, Hall F, Uhl G, Tanaka K, et al. Sigma1 receptor antagonists determine the behavioral pattern of the methamphetamine-induced stereotypy in mice. Psychopharmacology (Berl). 2009;203:781-92 pubmed publisher
  45. Okuyama S, Imagawa Y, Ogawa S, Araki H, Ajima A, Tanaka M, et al. NE-100, a novel sigma receptor ligand: in vivo tests. Life Sci. 1993;53:PL285-90 pubmed
    ..NE-100 failed to induce catalepsy in rats. These findings indicate that NE-100 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics. ..
  46. Lysko P, Yue T, Gu J, Feuerstein G. Neuroprotective mechanism of (+)SKF 10,047 in vitro and in gerbil global brain ischemia. Stroke. 1992;23:1319-23; discussion 1324 pubmed
    ..Neuroprotection by (+)SKF 10,047 most likely involves interaction at the N-methyl-D-aspartate receptor. These results suggest that the benzomorphan class of sigma-agonists may provide neuroprotection in cerebral ischemia and stroke. ..
  47. Tyler C, Bidlack J. Inhibition of (+)[3H]SKF 10,047 binding to rat brain membranes by FAB fragments from a monoclonal antibody directed against the opioid receptor. Neurochem Res. 1988;13:729-35 pubmed
    ..The Fab fragments acted as noncompetitive inhibitors of (+)[3H]SKF 10,047 binding. A (+)SKF 10,047 binding site in rat brain appears to share a common structural domain with mu and delta opioid receptors. ..
  48. Willetts J, Balster R. Effects of competitive and noncompetitive N-methyl-D-aspartate (NMDA) antagonists in rats trained to discriminate NMDA from saline. J Pharmacol Exp Ther. 1989;251:627-33 pubmed
    ..The results provide further evidence for differences in the behavioral profiles of competitive and noncompetitive NMDA antagonists. ..
  49. Kamei J. [Possible role of sigma-receptors in the regulation of cough reflex, gastrointestinal and retinal function]. Nihon Yakurigaku Zasshi. 1999;114:35-41 pubmed
    ..It is possible that sigma-receptor ligands may be useful as therapeutic drugs against retinal disease with ischemia-induced neuronal cell death such as retinal artery occlusion, diabetes mellitus or glaucoma. ..
  50. Ceci A, Smith M, French E. Activation of the A10 mesolimbic system by the sigma-receptor agonist (+)SKF 10,047 can be blocked by rimcazole, a novel putative antipsychotic. Eur J Pharmacol. 1988;154:53-7 pubmed
    ..These data provide further evidence that rimcazole's novel pharmacologic profile may involve a blockade of sigma-receptors on mesocorticolimbic dopamine neurons. ..
  51. Ohno M, Watanabe S. Intrahippocampal administration of (+)-SKF 10,047, a sigma ligand, reverses MK-801-induced impairment of working memory in rats. Brain Res. 1995;684:237-42 pubmed
    ..These results suggest that activation of hippocampal sigma and PCP binding sites exerts antagonistic effects on working memory function, possibly through modulation of NMDA receptor-mediated glutamatergic neurotransmission. ..
  52. Matsuno K, Kobayashi T, Mita S. Involvement of sigma-receptors in the increase in contraction of mouse vas deferens induced by exogenous ATP. J Pharm Pharmacol. 1996;48:96-9 pubmed
    ..In addition, the present ranking order suggests that the sigma-receptor potentiating the ATP-induced twitch contraction at post-junctional sites may differ from the sigma 1- and/or sigma 2-receptor subtypes. ..
  53. Fox P, Connick J, Hanlon G, France L, Nicholson C. The lack of utility of the rat vas deferens as a functional bioassay for sigma ligands. Eur J Pharmacol. 1991;193:139-43 pubmed
    ..PCP, (+)-SK&F 10047 and (+/-)-pentazocine probably enhance neurogenic contractions in rat vas deferens primarily by inhibition of the neuronal uptake of noradrenaline. ..