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Title: Mechanisms of interaction between anticholinesterases and opioids upon rodent nociception
Author: Green, Paul G.
ISNI:       0000 0001 3517 2521
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1985
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The literature describing the role of the cholinergic system and opioids on antinociception is reviewed. The effects of anticholinesterase agents and drugs used in the treatment of anticholinesterase poisoning were studied for their effects on opioid antinociception and locomotion. In both mice and rats, the irreversible anticholinesterase, DFP, produced apparent antinociception, but only at doses which caused motor incapacitation. Pre-treatment with DFP potentiated the antinociceptive potency of the opioid drug alfentanil but had little effect on morphine or fentanyl using the hot-plate test in mice. The reversible anticholinesterases, neostigmine and pyridostigmine, did not affect alfentanil antinociception in this species. In rats, DFP potentiated alfentanil and fentanyl antinociception using the paw pressure test, but had no effect on morphine. In mice, drugs used to treat anticholinesterase poisoning (atropine, pralidoxime and diazepam) did not alter the effect of DFP on alfentanil antinociception. DFP produced a decrease in locomotor activity in mice which was reversed following atropine and pralidoxime administration. DFP decreased the hyperlocomotory activity of alfentanil in mice, probably by increasing alfentanil catatonia, but had little effect on morphine or fentanyl. When diazepam was administered as part of the treatment for anticholinesterase poisoning, locomotor scores of opioid treated mice were markedly reduced. In mice radiolabelled distribution studies showed that DFP treatment enhanced the entry of alfentanil into all brain regions, whilst morphine and fentanyl levels were unaltered. Studies on plasma protein binding of alfentanil showed this was, in part, due to a displacement of alfentanil bound to plasma proteins by DFP, enabling free drug to enter the brain. These studies suggest that fentanyl would least likely produce interaction in individuals poisoned by irreversible anticholinesterase agents. In addition, the new opioid drug, alfentanil, may be liable to interactions when used clinically with other drugs by displacement from plasma protein binding sites to alter its antinociceptive activity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Zoology