Effects of the potent analgesic enkephalin-catabolizing enzyme inhibitors RB101 and kelatorphan on respiration

  title={Effects of the potent analgesic enkephalin-catabolizing enzyme inhibitors RB101 and kelatorphan on respiration},
  author={Eliane Boudinot and Marie-Pierre Morin-Surun and Arthur S. Foutz and Marie Claude Fourni{\'e}-Zaluski and B. Roques and Monique Denavit-Saubi{\'e}},
Protection of endogenous enkephalin catabolism as natural approach to novel analgesic and antidepressant drugs
The promising data obtained for future development of a new class of analgesics devoid of morphine side effects are reviewed, which could be of major interest in a number of severe and chronic pain syndromes.
RB101-mediated protection of endogenous opioids: potential therapeutic utility?
Findings suggest that RB101 and other inhibitors of enkephalin-degrading enzymes may have potential as novel therapeutic compounds for the treatment of pain, depression, and anxiety.
Inhibitors of Enkephalin Catabolism
Typically, long-term administration of opiates leads to a reduction in the magnitude and duration of effects produced by a given dose (tolerance) and to physical dependence, a state manifested by
Enkephalinase inhibitors, potential therapeutics for the future treatment of diarrhea predominant functional gastrointestinal disorders
The review is to answer the question whether enkephalinase inhibitors may be helpful in the future treatment of diarrhea predominant functional GI disorders and to discuss the antidiarrheal and antinociceptive potential of enkephalins inhibitors.
Semicarbazide Substitution Enhances Enkephalins Resistance to Ace Induced Hydrolysis
It is confirmed that semicarbazide substitution on enkephalins yields ACE resistance antinociceptive peptides, nevertheless it may necessarily not enhance the peptides analgesic potencies.
Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain
The effects of Dual enkephalinase inhibitors and FAAH inhibitors are compared and the progress in their rational design is described, to consider the challenges in their clinical development and opportunities for combination therapies.


RB 101, A Purported Pro Drug Inhibitor of Enkephalin Metabolism, Is Antinociceptive in Pregnant Mice
The results suggest that drugs such as RB 101 may produce antinociception with minimal effects on respiration, and suggest that pregnancy-induced analgesia with an inhibitor of endogenous enkephalin metabolism may be possible.
Pulmonary opiate receptor activation evokes a cardiorespiratory reflex.
Respiratory and cardiovascular effects of the μ‐opioid receptor agonist [Lys7]dermorphin in awake rats
It is indicated that analgesic doses of [Lys7]dermorphin stimulate respiration by activating central μ1 opioid receptors and this respiratory stimulation involves a forebrain 5‐hydroxytryptaminergic excitatory pathway.
"Mixed inhibitor-prodrug" as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes.
The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 were three times greater than those of a similar combined dose of its two constitutive moieties, and the separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence.
Antinociceptive effect of systemic kelatorphan, in mononeuropathic rats, involves different opioid receptor types.