Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracerebroventricular (40-80 microgram) or i.p. (5-20 mg/kg) injection of leucine enkephalin 15 min before or after s.c. morphine administration resulted in a marked, dose-dependent enhancement of morphine analgesia as measured by the mouse tail-flick assay. Further, i.p. injection of leucine enkephalin (5 mg/kg) enhanced the analgesia produced by methadone and levorphanol in the tail-flick assay but not that by nalorphine in the abdominal constriction assay. Met- but not leu-enkephalin was an active analgesic in the abdominal constriction assay with the doses used. (D-Ala2, D-leu5)-enkephalin (1 mg/kg) treatment also markedly enhanced morphine analgesia. Similarly, administration of leucine enkephalin enhanced the development of acute tolerance and dependence produced by a single dose of morphine. Methionine enkephalin had no effect on any of the pharmacological responses produced by morphine, methadone or levorphanol. Morphine brain levels of mice after treatment with leucine or methionine enkephalin were found to be no different than those of saline-treated control animals. These results suggest that leucine enkephalin may be an important and potent physiological modulator of narcotic efficacy.
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PMID:Differential effects of leucine and methionine enkephalin on morphine-induced analgesia, acute tolerance and dependence. 56 99

The binding of three tritiated opioid agonists--dihydromorphine, D-ala2-D-leu5-enkephalin and ethylketocyclazocine--was subjected to competition by unlabeled beta-endorphin, dynorphin-(1-13), and various fragments of these peptides, and the results analyzed by a computer program that we developed in an earlier study [11]. Peptides in both groups bound with highest affinity to sites 1 and 3 in our 4-site model, corresponding to the mu and delta sites of conventional classifications, with the dynorphin peptides also interacting with site 2, the kappa site. These results are discussed in relationship to the possible biological roles of these peptides as analgesics or as modulators of analgesia.
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PMID:Computer analysis of the effect of beta-endorphin and dynorphin and related compounds on opioid binding to mouse brain membrane. 256 53

The high-affinity mu-1 opioid binding site has been implicated in some opioid responses (e.g., supraspinal analgesia) but not others (e.g., respiratory depression) by comparing the actions of naloxone, a short-acting, non-selective antagonist, and naloxonazine, an irreversible and selective mu-1 antagonist. The mu-1 site has been implicated in the opioid component modulating free feeding and deprivation-induced feeding, but not glucoprivic feeding. The present study compared naloxone and naloxonazine antagonism of hyperphagia induced by morphine, ethylketocyclazocine (EKC), dynorphin and d-ala2,d-leu5-enkephalin (DADL) in rats. Morphine produced a dose-dependent (0.01-5 mg/kg) hyperphagia in mildly food-deprived rats that was blocked by naloxone (0.01-10 mg/kg). Naloxonazine (10 mg/kg) shifted the morphine hyperphagia dose-response curve to the right. These effects could not be fully accounted for by the intrinsic hypophagic properties of these antagonists. EKC produced a dose-dependent (0.5-5 mg/kg) hyperphagia which was blocked by naloxone (10 mg/kg) only at low effective EKC doses. Naloxonazine (10 mg/kg) failed to affect EKC hyperphagia. Naloxone, but not naloxonazine also blocked dynorphin and DADL hyperphagia. These results indicate that feeding induced by opiate and opioid agonists are differentially mediated by the mu-1 and other opioid binding sites; these data contrast with the modulation by the mu-1 site of the supraspinal analgesia induced by each of these agonists.
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PMID:Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine. 289 39

In previous studies, we observed that dynorphin- (1-13), but not dynorphin-(1-9), can significantly inhibit morphine- or beta-endorphin-induced analgesia despite not having any appreciable analgesic activity itself. Dynorphin-(1-13) showed no inhibitory effect on Sandoz FK33824-induced analgesia. In the present study, we examined the effect of dynorphin on morphine-, beta-endorphin-, D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia in both naive, morphine-tolerant and morphine-dependent mice. It was found that although dynorphin may inhibit morphine- or beta-endorphin-induced analgesia in naive animals, the peptide is not effective in inhibiting D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia. Dynorphin is also effective in blocking spontaneous withdrawal jumping in morphine-dependent animals. It is suggested that dynorphin-(1-13) may play a modulatory role in regulating analgesia due to morphine or beta-endorphin, but not that due to enkephalin. The action of peptides on morphine- or beta-endorphin-induced analgesia in the naive state is different from that of the tolerant state, suggesting that dynorphin may be involved in the development of morphine tolerance and physical dependence.
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PMID:Possible regulatory role of dynorphin on morphine- and beta-endorphin-induced analgesia. 611 98

Treatment with the enzyme arylsulfatase in vivo selectively attenuated the effect of analgesia induced by morphine, beta-endorphin or ethylketocyclazocine but not that induced by Sandoz FK33824 or D-ala2-D-leu5-enkephalin. The effect on morphine analgesia was indicated both by an increased morphine ED50 in the presence of a fixed dose of naloxone and by a decreased naloxone ED50 in the presence of a fixed dose of morphine. Arylsulfatase treatment in vivo also selectively affected in vitro ligand binding; Bmax values of the low affinity binding site of dihydromorphine, naloxone, D-ala2-D-leu5-enkephalin, D-ala2-met5-enkephalinamide and ethylketocyclazocine were decreased significantly while the Bmax values of the high affinity sites as well as the KD values of both the high and low affinity sites were affected little or not at all. The data suggest that the change induced by the enzyme may have been due to the alteration of certain constituents of the low affinity opiate binding site.
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PMID:Differential modification of opiate receptor activity by arylsulfatase treatment. 613 34

Receptor mechanisms for opiate induced respiratory depression and analgesia (tail-flick) were studied by the ED50 ratios and the apparent pA2 values of the interactions of naloxone with the mu-agonists morphine and D-ala2-me-phe4-met (O)ol5-enkephalin (FK-33824), and the delta-agonists D-ala2-D-leu5-enkephalin (DADL) and tyr-D-ser-gly-phe-leu-thr. The apparent pA2 values of morphine, FK-33824 and DADL for analgesia were similar, whereas the apparent pA2 values of the mu-agonists for respiratory depression were significantly lower than those of the delta-agonists. The ratio between the ED50 of FK-33824 in analgesia and respiratory depression was much lower than that of DADL. It is concluded that different receptors mediate the opiate-induced respiratory depression. One difficulty with the delta-receptors being maximally involved in this action is the high degree of antagonism shown by naloxone on the respiratory effects of the delta-agonists.
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PMID:Comparative effects of opioid peptides on respiration and analgesia in rats. 629 13

Continuous 2-15 Hz or 2 Hz electroacupuncture (EA) of 6 h applied to rats resulted in electroacupuncture tolerance (ET). The effect of 2-15 Hz ET on the recovery of mean arterial blood pressure (MAP) and heart rate (HR) of rats after hemorrhagic shock, and the effect of intrathecal (i.t.) injection of [D-ala2, D-leu5]enkephalin (DADLE) on MAP and HR of 2 Hz ET rats were observed. The results were as follows: 1) there was no dramatic difference between the 2-15 Hz ET group and the control group in the recovery of MAP and HR from hemorrhagic shock; 2) DADLE (25 micrograms) caused almost the same depressor effect in the 2 Hz ET group as that in the control group. These data suggest that the spinal lateral horn cells (supposed to be involved in regulating blood pressure) are insensitive to EA and cannot be made tolerant to continuous EA, which is different from the dorsal horn cell (supposed to be involved in analgesia).
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PMID:Effect of electroacupuncture tolerance by different frequencies on the opioid inhibition to cardiovascular activity in the spinal cord of rats. 802 11