The
pain relieving properties of
imipramine (100 mg orally),
tramadol (150 mg orally), and
anpirtoline (60 mg orally) were compared in 16 healthy subjects in a cross-over, double-blind, randomized, and placebo-controlled study.
Anpirtoline exhibits
analgesia which is possibly mediated via serotoninergic pathways, whereas
tramadol exerts its effects at
opioid receptors. The
pain-relieving effect of the
tricyclic antidepressant imipramine may involve both serotoninergic and
opioid mechanisms. Chemo-somatosensory event-related potentials (CSSERP) were recorded after painful stimulation of the nasal mucosa with
carbon dioxide. Subjects rated the perceived intensity of the stimuli by means of a visual analogue scale. In addition, acoustically evoked responses were recorded, the spontaneous EEG was analyzed in the frequency domain, the subjects' vigilance was assessed in a tracking task, and side effects of the drugs were monitored.
Anpirtoline and
tramadol produced a decrease of both CSSERP amplitudes and subjective estimates of
pain, the effects of the former compound being greater. In contrast, after administration of
imipramine no change of CSSERP amplitudes could be detected, whereas the subjective estimate of
pain intensity decreased significantly. This was accompanied by a significant decrease of arousal indicating that
pain relief produced by acute administration of
imipramine was primarily related to its sedation action. The
analgesic properties of
anpirtoline were demonstrated in man.
Tramadol was characterized as a week
opioid analgesic. In contrast,
imipramine appeared to produce its
pain-relieving effects predominantly by non-specific actions. It is hypothesized that different
analgesics may change ERP sources in a
drug-specific manner.