The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice

Maninder Malik, Claudia Rangel-Barajas, Robert H. Mach, Robert T. Luedtke

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds.

Original languageEnglish
Pages (from-to)136-144
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume148
DOIs
StatePublished - 1 Sep 2016

Fingerprint

Head
Receptor, Serotonin, 5-HT2C
sigma Receptors
sigma-1 receptor
N-(1-benzylpiperidin-4-yl)phenylacetamide
4-iodoamphetamine
Inbred DBA Mouse
Dopamine D2 Receptors
Dopamine Receptors
Neuroprotective Agents
Haloperidol
N-Methyl-D-Aspartate Receptors
sigma-2 receptor

Keywords

  • 2,5-dimethoxy-4-iodoamphetamine (DOI)
  • Antipsychotic activity
  • Head twitch response
  • Neuropsychiatric disorders
  • Sigma-1 receptors

Cite this

@article{cec0b0b611064a85b610484646356f94,
title = "The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice",
abstract = "Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds.",
keywords = "2,5-dimethoxy-4-iodoamphetamine (DOI), Antipsychotic activity, Head twitch response, Neuropsychiatric disorders, Sigma-1 receptors",
author = "Maninder Malik and Claudia Rangel-Barajas and Mach, {Robert H.} and Luedtke, {Robert T.}",
year = "2016",
month = "9",
day = "1",
doi = "10.1016/j.pbb.2016.07.001",
language = "English",
volume = "148",
pages = "136--144",
journal = "Pharmacology, Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",

}

The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice. / Malik, Maninder; Rangel-Barajas, Claudia; Mach, Robert H.; Luedtke, Robert T.

In: Pharmacology Biochemistry and Behavior, Vol. 148, 01.09.2016, p. 136-144.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice

AU - Malik, Maninder

AU - Rangel-Barajas, Claudia

AU - Mach, Robert H.

AU - Luedtke, Robert T.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds.

AB - Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds.

KW - 2,5-dimethoxy-4-iodoamphetamine (DOI)

KW - Antipsychotic activity

KW - Head twitch response

KW - Neuropsychiatric disorders

KW - Sigma-1 receptors

UR - http://www.scopus.com/inward/record.url?scp=84978957713&partnerID=8YFLogxK

U2 - 10.1016/j.pbb.2016.07.001

DO - 10.1016/j.pbb.2016.07.001

M3 - Article

VL - 148

SP - 136

EP - 144

JO - Pharmacology, Biochemistry and Behavior

JF - Pharmacology, Biochemistry and Behavior

SN - 0091-3057

ER -