Central nervous system activity of a Tabernaemontana arborea alkaloid extract involves serotonergic and opioidergic neurotransmission in murine models.

An alkaloid extract from the root bark of the Mexican tree Tabernaemontana arborea contains several monoterpenoid indole alkaloids, including voacangine, ibogaine, vobasine, coronaridine, and ibogamine. In murine models, the extract produced dose- and receptor-dependent antidepressant-like effects at low doses (0.1 to 1 mg/kg) via 5-HT1A receptors and antinociceptive effects at higher doses (30 and 56.2 mg/kg) via opioid receptors, without impairing motor coordination, ambulatory activity, or memory. Electroencephalography showed central nervous system depressant activity at the highest doses. The alkaloid mixture may hold therapeutic value for pain relief and psychiatric conditions without neurotoxic effects at effective doses.

Study at a glance

Abstract

Tabernaemontana arborea (Apocynaceae) is a Mexican tree species known to contain ibogan type alkaloids. This study aimed at determining central nervous system-related activities of an alkaloid extract obtained from the root bark of T. arborea. A gas chromatography-mass spectrometry (GC-MS) analysis was performed to describe the alkaloid profile of the extract. A wide dosing range (0.1 to 56.2 mg/kg) of this extract was evaluated in different murine models. Electrical brain activity was examined by electroencephalography (EEG). The extract's effects on motor coordination, ambulatory activity, and memory were analyzed based on the rotarod, open field (OFT), and object recognition tests (ORT), respectively. Antidepressant and antinociceptive activities were determined using the forced swimming test (FST) and the formalin assay, respectively. In order to elucidate the underlying mechanisms of action, the 5-HT1A receptor antagonist WAY100635 (1 mg/kg) or the opioid receptor antagonist naloxone (1 mg/kg) was included in the latter experiments. GC-MS analysis (μg/mg extract) confirmed the presence of the monoterpenoid indole alkaloids (MIAs) voacangine (207.00), ibogaine (106.33), vobasine (72.81), coronaridine (30.72), and ibogamine (24.2) as principal constituents of the extract, which exhibited dose- and receptor-dependent antidepressant (0.1 to 1 mg/kg; 5-HT1A) and antinociceptive (30 and 56.2 mg/kg; opioid) effects, without altering motor coordination, ambulatory activity, and memory. EEG indicated CNS depressant activity at high doses (30 and 56.2 mg/kg). The root bark of T. arborea contains a mixture of alkaloids that may hold therapeutic value in pain relief and the treatment of psychiatric diseases without causing neurotoxic activity at effective doses.