Morphine analgesia after intrathecal administration of a narcotic agonist, chloroxymorphamine and antagonist, chlornaltrexamine.

  title={Morphine analgesia after intrathecal administration of a narcotic agonist, chloroxymorphamine and antagonist, chlornaltrexamine.},
  author={A. Larson and M. Armstrong},
  journal={European journal of pharmacology},
  volume={68 1},
Abstract The spinal effects of two opiate compounds with nonequilibrium properties, chloroxymorphamine (COA) and chlornaltrexamine (CNA), were studied in the rat. Permanent indwelling cannulas to the spinal subarachnoid space allowed repeated injections of drugs to be made into a circumscribed receptor population. At various times after injection of the alkylating agents, the analgesic efficacy of morphine was measured. A single intrathecal injection of the antagonist, CNA, was found to… Expand
Spinal antagonism of tolerance and dependence induced by systemically administered morphine.
The spinal cord plays a significant role in development of tolerance and dependence induced by systemically administered opiates, and treatment with beta-CNA before morphine treatment antagonized naloxone-induced expression of withdrawal. Expand
Hyperalgesia produced by the intrathecal administration of tryptamine to rats
The results suggest that tryptamine, although it differs from serotonin by only one hydroxyl group, may play a role in nociception which is opposite that played by serotonin. Expand
Nociception is enhanced by the intrathecal injection of 5-methoxy-N,N-dimethyltryptamine in the rat
The ability of 5-MeODMT to mimic the facilitatory effect on nociception of similar doses of tryptamine, in contrast to the antinociceptive (analgesic) effect of serotonin, suggests an interaction of 5/N,N-dimethyltryptamine with tryptaminergic rather than serotonergic receptors in the spinal cord. Expand
Distribution of CNS Sites Sensitive to Tryptamine and Serotonin in Pain Processing
Areas sensitive to the antinociceptive effect of intrathecally (IT) administered serotonin (5HT) were compared to sites most sensitive to the hyperalgesic effect of IT tryptamine (TA).Expand
Serotonin-induced gnawing in rats: Comparison with tail pinch-induced gnawing
The ability of serotonin to elicit gnawing when injected at the spinal cord level, but to inhibit the same behavior when evoked by tail pinch, suggest that this neurotransmitter plays opposite roles depending on which part of the CNS is involved. Expand
Pharmacological profiles of β-funaltrexamine (β-FNA) and β-chlornaltrexamine (β-CNA) on the mouse vas deferens preparation
The profiles of action of beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) have been assessed in the mouse vas deferens preparation. beta-FNA, but not beta-CNA, demonstrated aExpand
Guidelines for the Synthesis of Small‐Molecule Irreversible Probes Targeting G Protein‐Coupled Receptors
Insight is provided into universal strategies and guidelines to successfully synthesize irreversible probes that target G protein‐coupled receptors (GPCRs) and an overview of commonly used chemoreactive and photoreactive groups is provided, and a comparison of their properties and potential applications is made. Expand
Opioid peptides: medicinal chemistry.


Induction of tolerance and withdrawal in rats receiving morphine in the spinal subarachnoid space.
The development of tolerance, as manifested in a reduction of the analgetic efficacy of these injections on the hot plate and tail flick, occurred in a dose dependent fashion over a period of 7 days, and revealed the existence of a two way cross tolerance between spinal and systemically administered morphine. Expand
Chronic catheterization of the spinal subarachnoid space
Calibration experiments revealed that there was little rostro-caudal diffusion of the injectate along the spinal axis and that even for compounds such as naloxone which can rapidly permeate neural tissues, the levels which do appear in the brain are small following the spinal subarachnoid administration of the drug. Expand
Antinociceptive Effect of Intrathecally Administered Serotonin
Serotonin, 100 or 200 µg, administered into the lumbar intrathecal space, produced an analgesic effect for as long as 40 minutes, and behavioral and morphologic observations after serotonin injections showed no adverse reaction. Expand
Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.
Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. Expand
Analgesia mediated by a direct spinal action of narcotics.
Narcotic analgetics administered directly into the spinal subarachnoid space of the rat via a chronically inserted catheter produce a potent analgesia that can be antagonized by naloxone. TheExpand
Chloroxymorphamine, and opioid receptor site-directed alkylating agent having narcotic agonist activity.
Chloroxymorphamine, the 6beta-N,N-bis(2-chloroethyl) derivative of oxymorphone, is a potent nonequilibrium narcotic agonist in the longitudinal muscle preparation of guinea pig ileum. TheExpand
Narcotic analgetics: CNS sites and mechanisms of action as revealed by intracerebral injection techniques
Experimental approaches are resorted to which permit a detailed study of the interaction between narcotic analgetics and particular regions and/or functional systems within the central nervous system. Expand
A simple, rapid method for determining the pain threshold in the rat was applied to the determination of analgesic properties of several substances, including cobra venom, where no analgesic property in the latter could be demonstrated. Expand
A simplified method of evaluating dose-effect experiments.
The method provides means for the rapid test of parallelism of two curves and easy computation of relative potency with its confidence limits and its accuracy is commensurate with the nature of dose-per cent effect data. Expand
Spinal serotonin terminal system mediates antinociception.
  • T. Yaksh, P. Wilson
  • Medicine
  • The Journal of pharmacology and experimental therapeutics
  • 1979