Faculty Collaboration Database

Identification of antidepressant drug leads through the evaluation of marine natural products with neuropsychiatric pharmacophores. Pharmacol Biochem Behav 2008 Mar;89(1):46-53

Date

11/27/2007

Pubmed ID

18037479

Pubmed Central ID

PMC4480916

DOI

10.1016/j.pbb.2007.10.021

Scopus ID

2-s2.0-38049153250 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

The marine environment is a valuable resource for drug discovery due to its diversity of life and associated secondary metabolites. However, there is very little published data on the potential application of marine natural products to treat neuropsychiatric disorders. Many natural products derived from chemically defended organisms in the marine environment have pharmacophores related to serotonin or clinically utilized antidepressant drugs. Therefore, in the present study, compounds selected for their structural similarity to serotonin or established antidepressants were evaluated for antidepressant-like activity using the forced swim and tail suspension tests in mice. The antidepressant positive controls, citalopram (selective serotonin reuptake inhibitor) and despiramine (tricyclic antidepressant) both dose-dependently reduced immobility time in the forced swim and tail suspension tests. Two marine natural product compounds tested, aaptamine and 5,6-dibromo-N,N-dimethyltryptamine, also produced significant antidepressant-like activity in the forced swim test. In the tail suspension test, the antidepressant-like effects of 5,6-dibromo-N,N-dimethyltryptamine were confirmed, whereas aaptamine failed to produce significant results. None of the tested compounds induced hyperlocomotion, indicating that nonspecific stimulant effects could not account for the observed antidepressant-like actions of the compounds. These studies highlight the potential to rationally select marine derived compounds for treating depression and other neuropsychiatric disorders.

Author List

Diers JA, Ivey KD, El-Alfy A, Shaikh J, Wang J, Kochanowska AJ, Stoker JF, Hamann MT, Matsumoto RR

Author

Abir El-Alfy PhD Assistant Dean, Professor in the School of Pharmacy Operations department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antidepressive Agents
Antidepressive Agents, Tricyclic
Biological Products
Citalopram
Desipramine
Drug Evaluation, Preclinical
Hindlimb Suspension
Male
Mice
Mice, Inbred DBA
Motor Activity
Swimming