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Potential antidepressant effects of novel tropane compounds, selective for serotonin or dopamine transporters.
J Pharmacol Exp Ther. 1997 Aug; 282(2):727-33.JP

Abstract

The forced swimming test (FST) predicts the efficacy of clinically effective antidepressants. In the present study, using the FST we examined the antidepressant potential of three novel tropane analogs: 8-methyl-2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicy clo[3.2.1] (WF-31) and 2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicyclo[3.2.1 ]octane (WF-50), selective inhibitors of serotonin uptake, and 8-methyl-2beta-propanoyl-3beta-(4-(1-methylphenyl)-8-azabicyclo[3. 2.1] octane (PTT, WF-11), a selective inhibitor of dopamine uptake. Fluoxetine and GBR 12909 were used as controls for selective inhibitors of serotonin and dopamine, respectively. Drugs were administered three times in a 24-hr period between pretest and test sessions. Intraperitoneal administration of WF-31 (0.1-10.0 mg/kg), WF-50 (0.3-10.0 mg/kg) and fluoxetine (0.3-10.0 mg/kg) dose-dependently decreased immobility while increasing swimming. In contrast, WF-11 (0.3-3.0 mg/kg) dose-dependently decreased immobility and increased both swimming and climbing, whereas GBR 12909 (3.0-30.0 mg/kg) decreased immobility, increased climbing but did not affect swimming. In a separate experiment, WF-11 (1.0 mg/kg) increased locomotor activity, whereas a higher dose of WF-11 (3.0 mg/kg) and GBR-12909 (30.0 mg/kg) produced stereotypic behaviors, suggesting that the effects in the FST may have been attributable to increases in general activity. However, the effects of WF-11 on swimming in the FST indicate that WF-11 produces antidepressant-like effects in addition to motor stimulation. These results confirm previous results that behavioral patterns manifested in the FST are characteristic of specific monoamine uptake inhibitors. In addition, these results demonstrate that WF-31 and WF-50 produce behavioral patterns similar to fluoxetine in the FST without accompanying decreases in motor activity, suggesting a potential antidepressant action. Based on comparisons with fluoxetine, the data suggest WF-31 and WF-50 may be therapeutically useful as potential antidepressant medications.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Center for the Neurobiological Investigation of Drug Abuse, Wake Forest University, Winston-Salem, North Carolina, USA. hemby@pharm.med.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9262336

Citation

Hemby, S E., et al. "Potential Antidepressant Effects of Novel Tropane Compounds, Selective for Serotonin or Dopamine Transporters." The Journal of Pharmacology and Experimental Therapeutics, vol. 282, no. 2, 1997, pp. 727-33.
Hemby SE, Lucki I, Gatto G, et al. Potential antidepressant effects of novel tropane compounds, selective for serotonin or dopamine transporters. J Pharmacol Exp Ther. 1997;282(2):727-33.
Hemby, S. E., Lucki, I., Gatto, G., Singh, A., Thornley, C., Matasi, J., Kong, N., Smith, J. E., Davies, H. M., & Dworkin, S. I. (1997). Potential antidepressant effects of novel tropane compounds, selective for serotonin or dopamine transporters. The Journal of Pharmacology and Experimental Therapeutics, 282(2), 727-33.
Hemby SE, et al. Potential Antidepressant Effects of Novel Tropane Compounds, Selective for Serotonin or Dopamine Transporters. J Pharmacol Exp Ther. 1997;282(2):727-33. PubMed PMID: 9262336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential antidepressant effects of novel tropane compounds, selective for serotonin or dopamine transporters. AU - Hemby,S E, AU - Lucki,I, AU - Gatto,G, AU - Singh,A, AU - Thornley,C, AU - Matasi,J, AU - Kong,N, AU - Smith,J E, AU - Davies,H M, AU - Dworkin,S I, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 727 EP - 33 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 282 IS - 2 N2 - The forced swimming test (FST) predicts the efficacy of clinically effective antidepressants. In the present study, using the FST we examined the antidepressant potential of three novel tropane analogs: 8-methyl-2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicy clo[3.2.1] (WF-31) and 2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicyclo[3.2.1 ]octane (WF-50), selective inhibitors of serotonin uptake, and 8-methyl-2beta-propanoyl-3beta-(4-(1-methylphenyl)-8-azabicyclo[3. 2.1] octane (PTT, WF-11), a selective inhibitor of dopamine uptake. Fluoxetine and GBR 12909 were used as controls for selective inhibitors of serotonin and dopamine, respectively. Drugs were administered three times in a 24-hr period between pretest and test sessions. Intraperitoneal administration of WF-31 (0.1-10.0 mg/kg), WF-50 (0.3-10.0 mg/kg) and fluoxetine (0.3-10.0 mg/kg) dose-dependently decreased immobility while increasing swimming. In contrast, WF-11 (0.3-3.0 mg/kg) dose-dependently decreased immobility and increased both swimming and climbing, whereas GBR 12909 (3.0-30.0 mg/kg) decreased immobility, increased climbing but did not affect swimming. In a separate experiment, WF-11 (1.0 mg/kg) increased locomotor activity, whereas a higher dose of WF-11 (3.0 mg/kg) and GBR-12909 (30.0 mg/kg) produced stereotypic behaviors, suggesting that the effects in the FST may have been attributable to increases in general activity. However, the effects of WF-11 on swimming in the FST indicate that WF-11 produces antidepressant-like effects in addition to motor stimulation. These results confirm previous results that behavioral patterns manifested in the FST are characteristic of specific monoamine uptake inhibitors. In addition, these results demonstrate that WF-31 and WF-50 produce behavioral patterns similar to fluoxetine in the FST without accompanying decreases in motor activity, suggesting a potential antidepressant action. Based on comparisons with fluoxetine, the data suggest WF-31 and WF-50 may be therapeutically useful as potential antidepressant medications. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9262336/Potential_antidepressant_effects_of_novel_tropane_compounds_selective_for_serotonin_or_dopamine_transporters_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9262336 DB - PRIME DP - Unbound Medicine ER -