title: 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.
authors.affiliation: Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. pgerner@partners.org
authors.forename: Peter
authors.initials: P
authors.lastname: Gerner
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Srinivasa
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Zizza
authors.forename: Zhi-Ye
authors.initials: ZY
authors.lastname: Zhuang
authors.forename: ShiHua
authors.initials: S
authors.lastname: Luo
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Sunil
authors.initials: S
authors.lastname: Eappen
authors.forename: GingKuo
authors.initials: G
authors.lastname: Wang
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004316:Doxepin / Q000008:administration & dosage*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004316:Doxepin