Planta Med 2008; 74 - P-61
DOI: 10.1055/s-2008-1075257

Pharmacological Investigation of Observed Anxiolytic Effects of the Marine Natural Product Aaptamine

JJ Bowling 1, VT Karamyan 2, RC Speth 2, 4, KJ Sufka 2, 3, 4, MT Hamann 1, 3, 4
  • 1Department of Pharmacognosy, The University of Mississippi, University, Mississippi, 38677, USA
  • 2Department of Pharmacology, The University of Mississippi, University, Mississippi, 38677, USA
  • 3Department of Psychology, The University of Mississippi, University, Mississippi, 38677, USA
  • 4Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, Mississippi, 38677, USA

Aaptamine, 8,9-dimethoxy-4H-benzo[de][1,6]naphthyridine, is isolated in significant amounts from the marine sponge Aaptos sp. and exhibits broad activity against a number of in vitro receptors and whole cell targets [1]. The benzonapthyridine core is unique in nature and contains structural characteristics of dopamine. This structural characteristic corresponds to recently reported data that claims anti-depressant effects of aaptamine in mouse forced swim tests [2]. Aaptamine was administered in three doses (5, 10, 15 mg/kg i.m.) and the mice were observed for anxiolytic effects in an established chick social separation-stress model [3]. Results showed that separation-induced distress vocalizations were significantly attenuated in isolated chicks receiving 10 or 15 mg/kg aaptamine (ns = 12; ps < 0.05). However, higher concentrations of aaptamine were reported to induce a transient sedative state followed by motor incoordination. Thus the anxiolytic effects reported at the lower doses may be related to aaptamine's other behavioral effects. In an effort to identify receptor system(s) mediating this behavior, aaptamine was tested for its ability to compete for µ-, δ- and κ-opioid receptor binding (vs. 3H-DAMGO, 3H-DPDPE and 3H–U69593 respectively) in rat brain membranes. The results of receptor binding assays indicated low affinity of aaptamine for all three opioid receptors with Ki values 1.49 ± 0.07 µM for µ- and > 5 µM for δ- and κ-opioid receptors. Acknowledgements: The project described was supported by Grant Number P20RR021929 from the National Center For Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. This investigation was conducted in a facility constructed with support from research facilities improvement program C06 RR-14503-01 from the NIH National Center for Research Resources. References: [1] Bowling J, et al. (2008) Chem. Biol. Drug Disc. (Epub) [2] Diers J, et al. (2007) Pharmacol Biochem Behav. (Epub) [3] Feltenstein M, et al. (2004) Pharmacol Biochem Behav. 77(2): 221–6.