An α2-adrenoceptor agonist,
clonidine, is extensively used in both
anesthesia and
intensive care medicine. However,
clonidine may produce pronounced hemodynamic side effects such as
hypotension and
bradycardia which may limit its usefulness in certain conditions.
Fadolmidine is a potent α2-adrenoceptor agonist with different physicochemical properties than
clonidine. Here, the effects of
fadolmidine and
clonidine on
analgesia (an increase in thermal skin twitch response latency), sedation, blood pressure, heart rate, respiratory rate, and body temperature were evaluated either up to 8 h after either intrathecal or epidural bolus
injections or during a 24-h continuous intrathecal infusion at equipotent
analgesic doses in non-anesthetized Beagle dogs.
Fadolmidine and
clonidine produced a dose-dependent and equipotent maximal antinociception after intrathecal bolus injection (ED50: 67 μg and 78 μg, respectively), but the duration of action of
fadolmidine was more long-lasting. During the intrathecal infusion,
fadolmidine achieved a good
analgesic effect without evoking cardiovascular side effects, e.g.,
hypotension; these were evident during
clonidine infusion. Epidurally, the antinociceptive potency of
fadolmidine was weaker (ED50: 128 μg) than when intrathecally administered and weaker than that of epidural
clonidine (ED50: 51 μg). At
analgesic doses,
fadolmidine injection induced moderate initial
hypertension concomitantly with a decrease in heart rate whereas
clonidine evoked
hypotension and
bradycardia. These results suggest that especially when non-
opioid long-term
pain relief is needed, an intrathecal infusion of
fadolmidine can provide long-term antinociception with less of the known use-limiting adverse effects associated with
clonidine.