title: Intrathecal antinociceptive interaction between the NMDA antagonist ketamine and the opioids, morphine and biphalin.
abstract: Biphalin is an opioid peptide analogue that currently is under clinical development as a new type of site-directed analgesic. In rats, the intrathecal (i.t.) analgesic potency of biphalin is 1000-fold greater than morphine. Such a high activity may reflect this compound's activation of three types of opioid receptors (mu, delta and kappa). NMDA receptors also play an important role in nociceptive processing. Therefore, we investigated in rats whether an NMDA antagonist may influence biphalin-induced antinociception. In the present study, ketamine was chosen because of the widespread safe use of this drug in clinical practice. I.t. application of ketamine alone had relatively little analgesic effect and its excitatory effects limited possible doses of the drug. Co-administration of ketamine with biphalin or morphine produced markedly greater antinociception than biphalin or morphine alone in acute, thermal tail flick testing. These results suggest that NMDA antagonists may be useful potentiators of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect, lower doses of biphalin or morphine are required when ketamine is co-administered.
authors: Medical Research Centre, Polish Academy of Sciences, Pawinskiego Street 5, 02106 Warsaw, Poland.
authors: Dariusz
authors: D
authors: Kosson
authors: Anna
authors: A
authors: Klinowiecka
authors: Piotr
authors: P
authors: Kosson
authors: Iwona
authors: I
authors: Bonney
authors: Daniel B
authors: DB
authors: Carr
authors: Ewa
authors: E
authors: Mayzner-Zawadzka
authors: Andrzej W
authors: AW
authors: Lipkowski
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D004745:Enkephalins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006358:Hot Temperature / Q000009:adverse effects; D007278:Injections, Spinal; D007649:Ketamine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009271:Naltrexone / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D013623:Tail
chemical_list: D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D004745:Enkephalins; D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D009271:Naltrexone; D007649:Ketamine; D009020:Morphine; C053673:biphalin