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Antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a putative trace amine receptor ligand involves l-arginine-nitric oxide-cyclic guanosine monophosphate pathway.
Neurosci Lett. 2011 Oct 03; 503(2):120-4.NL

Abstract

1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol is a novel putative trace amine receptor modulator hypothesized to be useful for treatment-resistant depression. In our previous study, we have demonstrated the antidepressant-like effect of this molecule in mouse forced swim and tail suspension tests and shown to act via modulating the levels of norepinephrine, serotonin and dopamine. The present study attempts to explore the involvement of l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol in the mouse forced swim test. The antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (8 mg/kg, i.p) was reversed by pretreatment with L-arginine (750 mg/kg, i.p.), a nitric oxide precursor. In contrast, pretreatment with methylene blue (a soluble guanlyate cyclase inhibitor and nitric oxide synthase (NOS) inhibitor) or 7-nitroindazole (a specific neuronal NOS inhibitor) potentiated the antidepressant-like effect of sub-effective dose of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (2mg/kg, i.p.) in this test model. Furthermore, the antidepressant-like effect of this molecule (8 mg/kg, i.p.) was reversed by sildenafil (5mg/kg, i.p.), a phosphodiesterase inhibitor. In conclusion, the antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol involved L-arginine-nitric oxide-cyclic guanosine monophospate signaling pathway.

Authors+Show Affiliations

Department of Neurology, University of California Davis Medical Center, Sacramento, CA 95816, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21875647

Citation

Dhir, Ashish, and S K. Kulkarni. "Antidepressant-like Effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a Putative Trace Amine Receptor Ligand Involves L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway." Neuroscience Letters, vol. 503, no. 2, 2011, pp. 120-4.
Dhir A, Kulkarni SK. Antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a putative trace amine receptor ligand involves l-arginine-nitric oxide-cyclic guanosine monophosphate pathway. Neurosci Lett. 2011;503(2):120-4.
Dhir, A., & Kulkarni, S. K. (2011). Antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a putative trace amine receptor ligand involves l-arginine-nitric oxide-cyclic guanosine monophosphate pathway. Neuroscience Letters, 503(2), 120-4. https://doi.org/10.1016/j.neulet.2011.08.020
Dhir A, Kulkarni SK. Antidepressant-like Effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a Putative Trace Amine Receptor Ligand Involves L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway. Neurosci Lett. 2011 Oct 3;503(2):120-4. PubMed PMID: 21875647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a putative trace amine receptor ligand involves l-arginine-nitric oxide-cyclic guanosine monophosphate pathway. AU - Dhir,Ashish, AU - Kulkarni,S K, Y1 - 2011/08/19/ PY - 2011/05/18/received PY - 2011/07/22/revised PY - 2011/08/11/accepted PY - 2011/8/31/entrez PY - 2011/8/31/pubmed PY - 2012/1/14/medline SP - 120 EP - 4 JF - Neuroscience letters JO - Neurosci. Lett. VL - 503 IS - 2 N2 - 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol is a novel putative trace amine receptor modulator hypothesized to be useful for treatment-resistant depression. In our previous study, we have demonstrated the antidepressant-like effect of this molecule in mouse forced swim and tail suspension tests and shown to act via modulating the levels of norepinephrine, serotonin and dopamine. The present study attempts to explore the involvement of l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol in the mouse forced swim test. The antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (8 mg/kg, i.p) was reversed by pretreatment with L-arginine (750 mg/kg, i.p.), a nitric oxide precursor. In contrast, pretreatment with methylene blue (a soluble guanlyate cyclase inhibitor and nitric oxide synthase (NOS) inhibitor) or 7-nitroindazole (a specific neuronal NOS inhibitor) potentiated the antidepressant-like effect of sub-effective dose of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (2mg/kg, i.p.) in this test model. Furthermore, the antidepressant-like effect of this molecule (8 mg/kg, i.p.) was reversed by sildenafil (5mg/kg, i.p.), a phosphodiesterase inhibitor. In conclusion, the antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol involved L-arginine-nitric oxide-cyclic guanosine monophospate signaling pathway. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/21875647/Antidepressant_like_effect_of_1__7_methoxy_2_methyl_1234_tetrahydro_isoquinolin_4_YL__cyclohexanol_a_putative_trace_amine_receptor_ligand_involves_l_arginine_nitric_oxide_cyclic_guanosine_monophosphate_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(11)01195-5 DB - PRIME DP - Unbound Medicine ER -