SYMMETRIC TOLERANCE AFTER CONTINUOUS SPINAL INFUSION OF MU AGONISTS IN RATS

1989 ◽  
Vol 71 (Supplement) ◽  
pp. A621
Author(s):  
M. Sosnowski ◽  
T. L. Yaksh
Keyword(s):  
Mu Agonists

Regulation of ventilation and oxygen consumption by delta- and mu-opioid receptor agonists

1985 ◽  
Vol 59 (3) ◽  
pp. 959-968 ◽  
Author(s):  
J. I. Schaeffer ◽  
G. G. Haddad
Keyword(s):  
Metabolic Rate ◽  
Minute Ventilation ◽  
Periodic Breathing ◽  
Receptor Agonists ◽  
Shallow Breathing ◽  
Stressful Stimulation ◽  
Alveolar Hypoventilation ◽  
Dose Dependent Decrease ◽  
Mu Agonists ◽  
Delta Receptor

To study the effect of endorphins on metabolic rate and on the relationship between O2 consumption (VO2) and ventilation, we administered enkephalin analogues (relatively selective delta-receptor agonists) and a morphiceptin analogue (a highly selective mu-receptor agonist) intracisternally in nine unanesthetized chronically instrumented adult dogs. Both delta- and mu-agonists decreased VO2 by 40–60%. delta-Agonists induced a dose-dependent decrease in mean instantaneous minute ventilation (VT/TT) associated with periodic breathing. The decrease in VT/TT started and resolved prior to the decrease and returned to baseline of VO2, respectively. In contrast, the mu-agonists induced an increase in VT/TT associated with rapid shallow breathing. Arterial PCO2 increased and arterial PO2 decreased after both delta- and mu-agonists. Low doses of intracisternal naloxone (0.002–2.0 micrograms/kg) reversed the opioid effect on VT/TT but not on VO2; higher doses of naloxone (5–25 micrograms/kg) reversed both. Naloxone administered alone had no effect on VT/TT or VO2. These data suggest that 1) both delta- and mu-agonists induce alveolar hypoventilation despite a decrease in VO2, 2) this hypoventilation results from a decrease in VT/TT after delta-agonists but an increase in dead space ventilation after mu-agonists, and 3) endorphins do not modulate ventilation and metabolic rate tonically, but we speculate that they may do so in response to stressful stimulation.

Opioid Pharmacology

2008 ◽  
Vol 2s;11 (3;2s) ◽  
pp. S133-S153 ◽  
Author(s):  
Andrea M. Trescot
Keyword(s):  
Side Effects ◽  
Pain Treatment ◽  
Volume Of Distribution ◽  
Opiate Withdrawal ◽  
Pharmacokinetic Parameters ◽  
Intractable Pain ◽  
Advantages And Disadvantages ◽  
Withdrawal Syndromes ◽  
The Individual ◽  
Mu Agonists

Background: Mu agonists have been an important component of pain treatment for thousands of years. The usual pharmacokinetic parameters (half-life, clearance, volume of distribution) of opioids have been known for some time. However, the metabolism has, until recently, been poorly understood, and there has been recent interest in the role of metabolites in modifying the pharmacodynamic response in patients, in both analgesia and adverse effects. A number of opioids are available for clinical use, including morphine, hydromorphone, levorphanol, oxycodone, and fentanyl. Advantages and disadvantages of various opioids in the management of chronic pain are discussed. Objective: This review looks at the structure, chemistry, and metabolism of opioids in an effort to better understand the side effects, drug interactions, and the individual responses of patients receiving opioids for the treatment of intractable pain. Conclusion: Mu receptor agonists and agonist-antagonists have been used throughout recent medical history for the control of pain and for the treatment of opiate induced side effects and even opiate withdrawal syndromes. Key words: Opioid metabolism, opioid interactions, morphine, codeine, hydrocodone, oxycodone, hydromorphone, methadone, intractable pain, endorphins, enkephalins, dynorphins, narcotics, pharmacology, propoxyphene, fentanyl, oxymorphone, tramadol

Differential antagonism of mu agonists by U50,488H in the rat

Life Sciences ◽  
1987 ◽  
Vol 41 (23) ◽  
pp. 2511-2516 ◽  
Author(s):  
Frank Porreca ◽  
Frank C. Tortella
Keyword(s):  
Mu Agonists

scholarly journals Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
S. Stevens Negus ◽  
Ember M. Morrissey ◽  
John E. Folk ◽  
Kenner C. Rice
Keyword(s):  
Rhesus Monkeys ◽  
Delta Opioid Receptor ◽  
Preclinical Models ◽  
Thermal Nociception ◽  
Mu Opioid ◽  
Opioid Agonists ◽  
Antinociceptive Effects ◽  
Mu Agonists ◽  
Opioid Receptor Agonists ◽  
Dose Dependent

Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of these mu agonists in rhesus monkeys (0.9 : 1 SNC80/methadone; 0.29 : 1 SNC80/morphine; 3.6 : 1 SNC80/nalbuphine). Methadone, morphine, and nalbuphine each produced dose-dependent antiallodynia. SNC80 produced partial antiallodynia up to the highest dose tested (5.6 mg/kg). SNC80 produced a modest, enantioselective, and naltrindole-reversible enhancement of methadone-induced antiallodynia. However, SNC80 did not enhance morphine antiallodynia and only weakly enhanced nalbuphine antiallodynia. Overall, SNC80 produced modest or no enhancement of the antiallodynic effects of the three mu agonists evaluated. These results suggest that delta agonist-induced enhancement of mu agonist antiallodynia may be weaker and less reliable than previously demonstrated enhancement of mu agonist acute thermal nociception.

Effects of various opiates including specific delta and mu agonists on dopamine release from nigrostriatal dopaminergic neurons in the rat and in the cat

Life Sciences ◽  
1982 ◽  
Vol 31 (20-21) ◽  
pp. 2291-2294 ◽  
Author(s):  
M.F. Chesselet ◽  
A. Cheramy ◽  
T.D. Reisine ◽  
C. Lubetzki ◽  
J. Glowinski ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Dopamine Release ◽  
Mu Agonists

Effect of endorphins on heart rate and blood pressure in adult dogs

1986 ◽  
Vol 250 (5) ◽  
pp. H796-H805 ◽  
Author(s):  
G. G. Haddad ◽  
H. J. Jeng ◽  
T. L. Lai
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Opioid Receptor ◽  
Time Course ◽  
Marked Change ◽  
Cardiovascular Function ◽  
Base Line ◽  
Mu Opioid ◽  
Arterial Blood ◽  
Mu Agonists

To investigate the role of opioids in regulating cardiovascular function, we administered delta-opioid receptor agonists D-Ala-D-Leu enkephalin (DADLE) and D-Ala-Met enkephalinamide (DAME), and mu-opioid receptor agonist, a morphiceptin analogue (MA), intracisternally in 13 unanesthetized, chronically instrumented adult dogs in 2 doses (25 and 125 micrograms/kg). After an initial transient drop, the R-R interval increased (peak approximately 25–60 min) postadministration of opioids. The time course and the magnitude of the change in R-R interval depended on the agonist: delta-agonists induced a more prolonged and marked change in R-R interval than mu-agonists at both doses. Mean arterial blood pressure (MAP) increased initially but dropped toward or even below base line 30 min after opioids administration. Atropine, given intravenously or intra-arterially at peak action of agonist in relatively low doses (0.02 mg/kg), induced an AV block followed by a marked decrease in R-R interval. There was also an increase in MAP after atropine. Naloxone, given intracisternally, reversed both delta- and mu-opioid effects but did not induce changes in the R-R interval without prior administration of opioids. We conclude that in unanesthetized adult dogs 1) both mu- and delta-receptor opioid agonists prolong the R-R interval, and this depends on the type of receptor stimulated; 2) opioids induce slowing in heart rate, possibly by increasing parasympathetic activity to the heart; 3) enkephalin and morphiceptin analogues induce a biphasic response in MAP; and 4) endorphins do not modulate cardiovascular function tonically; we speculate that they can alter the R-R interval and MAP in the presence of stimuli.

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