Pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, enhances the analgesic effect of tramadol.
The ability of pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, to enhance the clinical antidepressant response to selective serotonin re-uptake inhibitors is generally attributed to a blocking of the feedback that inhibits the serotoninergic neuronal activity mediated by somatodendritic 5-hydroxytryptamine (5-HT)(1A) autoreceptors. The current study examined the ability of pindolol to enhance the analgesic effect of tramadol, an atypical centrally-acting analgesic agent with relatively weak opioid receptor affinity and which, like some antidepressants, is able to inhibit the re-uptake of 5-HT in the raphe nuclei. Racemic pindolol (2 mg/kg, s.c.), rendered analgesic a non-effective acute dose of tramadol (10-40 mg/kg, i.p.) in two nociceptive tests: a hot plate test in mice and a plantar test in rats. Moreover, (+/-)8-OH-DPAT (0.125-1 mg/kg, s.c.), a selective 5-HT(1A) agonist, reduces the analgesic effect of tramadol in the same tests. These results suggest an implication of the somatodendritic 5-HT(1A) receptors in the analgesic effect of tramadol and open a new adjuvant analgesic strategy for the use of this compound.
Rojas-Corrales
Olga M
OM
Department of Neuroscience, Neuropsycopharmacology Unit, University of Cádiz, Plz. Fragela 9, 11003 Cádiz, Spain.
Ortega-Alvaro
Antonio
A
Gibert-Rahola
Juan
J
Roca-Vinardell
Aranzazu
A
Micó
Juan A
JA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D006358:Hot Temperature; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010869:Pindolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014147:Tramadol / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000701:Analgesics, Opioid; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D014147:Tramadol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol