Doxepin by Topical Application and Intrathecal Route in Rats

Abstract

The tricyclic antidepressant, doxepin, has been reported to be a potent local anesthetic in rat sciatic nerve blockade. We hypothesized that topical doxepin has significantly longer antinociception compared with control and intrathecally compared with bupivacaine. Solutions of 0.3 mL of doxepin at 50, 75, and 100 mM and control (only the vehicle solution) were applied as a patch to the shaved dorsal skin of rats. After a 2-h contact interval, the patch was removed, and the rats were tested by three sets of six pinpricks. Inhibition of withdrawal to pain and cutaneous trunci muscle reflex were graded. In the second investigation, 60 muL of doxepin at 10, 20, and 50 mM was injected through intrathecal catheters implanted in the lumbar region of rats, which were evaluated for motor function, proprioception, and nociception. Topical doxepin at concentrations of 75 mM and 100 mM was significantly more effective than control (P < 0.05). Complete recovery for the 100-mM concentration occurred at 60 h, although two of five rats demonstrated erythema and scarring. Intrathecally, 20 mM of doxepin was not significantly different for motor and proprioceptive function from 23 mM (0.75%) bupivacaine; however, neurotoxicity (defined as persistent neurological deficit) commenced at 50 mM.

Analgesic effects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain

“…Because there were no publications that directly compared these drugs, we focused on studies that topically administered these drugs in neuropathic pain models. Topically administered doxepin was effective, which is in accordance with the results from Gerner et al [44]. The same results were observed after amitriptyline administration.…”

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

“…From these results and at the doselevels assayed, amitriptyline seemed to elicit the lower analgesic effect. Doxepin was the most potent drug in both types of pain tested, as previously pointed out by other authors [56][57][58], but the great interest lays on the fact that its potency was considerably increased (62% and 229% in both pharmacodynamic experiments) when the drug was encapsulated. These outstanding results obtained for doxepin suggest that this drug should be considered as a therapeutical alternative in pain relieving.…”

Transcutaneous electroporation mediated delivery of doxepin-HPCD complex: A sustained release approach for treatment of postherpetic neuralgia

“…The pain avoiding response was indicated by withdrawal and vocalization of the animal. Three sets of six pinpricks were applied (at 2, 4, 6 h and every 12 h thereafter) at the test and control area and the number of pinpricks to which rat failed to respond were recorded on a scale of 0–6 [31, 32]. …”