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)

The potencies of the R and S isomers of thiorphan and rigid analogs of thiorphan to produce analgesia in a mouse hot-plate assay have been compared with their potencies to inhibit enkephalin degradation by rat brain "enkephalinase A." The R and S isomers of thiorphan were equipotent as enzyme inhibitors (IC50 approximately 10(-9) M) but had significantly different analgesic profiles when injected i.c.v. Rigid analogs of thiorphan were less potent enzyme inhibitors (IC50 values of 10(-7) - 10(-4) M) but produced analgesia and potentiated Tyr-D-Ala-Gly-Phe-Met-NH2 induced analgesia at doses (i.c.v.) comparable to thiorphan. These observations suggest that inhibitors of enkephalinase A produce analgesia through a pharmacological mechanism which is not directly related to inhibition of enkephalin degradation.
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PMID:Thiorphan and analogs: lack of correlation between potency to inhibit "enkephalinase A" in vitro and analgesic potency in vivo. 389 20

Phe-Met-Arg-Phe-NH2 (FMRF-NH2) was initially isolated from the macrocallista nimbosa clam and subsequently existence of FMRF-NH2-like immunoreactivity (FMRF-NH2-IR) was detected in mammalian CNS. Due to the structural similarity between FMRF-NH2 and the C-terminal extended form of met5-enkephalin, met5-enkephalin-arg6-phe7 (YGGFMRF), a possible interaction between these two peptides was explored. FMRF-NH2 injected intrathecally decreases the antinociceptive action of YGGFMRF or morphine. However, the FMRF-NH2-IR present in rat and bovine brains differs from FMRF-NH2. Intrathecally injected FMRF-NH2-IR partially purified from bovine brain reduces YGGFMRF antinociception. The antagonism elicited by FMRF-NH2 can be reversed by proglumide, which was reported to act as a CCK antagonist. In order to characterize the biological profile of FMRF-NH2-IR, the effect of proglumide and of the FMRF-NH2 antibody on morphine analgesia was tested. Both the IgG isolated from FMRF-NH2 antiserum and proglumide were found to potentiate the morphine analgesia. The results taken together suggest that endogenous FMRF-NH2-IR modulates opioid antinociception; perhaps by acting as an endogenous naloxone.
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PMID:Are Phe-Met-Arg-Phe-NH2 immunoreactive peptides endacoids modulating opiate antinociception? 390 60

Rats were taught to self-administer Leu-E (10, 25 and 100 micrograms/microliters) or Met-E (0.5, 10 and 100 micrograms/microliters) through a cannula implanted in the lateral cerebral ventricle (i.c.v.). Their self-injection behaviour was studied before, during and after nociceptive stimulation. In the course of the control period of the experiment, the rats rapidly learned lever pressing for self-injection of enkephalin but they did not increase their self-administration of Leu-E or Met-E during the nociceptive electrical stimulation period. Also studied were the acute effect of i.c.v. enkephalin and morphine on tail-flick latency (sec) and electrical threshold vocalization (mA). The analgesic effect of Leu-E and Met-E was of short duration (less than 2-6 min). The mean rise (i.e., analgesia) of the tail-flick threshold showed a significant difference after i.c.v. Met-E only. The acute i.c.v. effect of 20 or 30 micrograms of morphine induced a long-lasting analgesia, greater than 40 min. These results show that Leu-E and Met-E are not rewarding during a nociceptive stimulus. This may be due to the short and inconstant analgesic action of i.c.v. enkephalins.
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PMID:A study of intracerebroventricular self-administration of leucine or methionine enkephalin by rats in response to intermittent electric shocks. 401 Dec 83

Social conflict and defeat in mice leads to an activation of endogenous opiate systems. The effects of intracerebroventricular administration of the peptide FMRFamide (Phe-Met-Arg-Phe-NH2) and the opiate antagonist naloxone, on aggressive encounters, defeat-induced analgesia and defeat-induced feeding were examined in male mice. Both substances reduced the number of bites required to cause defeat in subordinate mice during aggressive encounters, as well as suppressing the subsequent defeat-induced analgesia. Administration of FMRFamide or naloxone also reduced defeat-induced feeding. These results indicate that FMRFamide (or FMRFamide-like neuropeptides) may function as endogenous opioid antagonists.
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PMID:FMRFamide, a putative endogenous opiate antagonist: evidence from suppression of defeat-induced analgesia and feeding in mice. 408 Jan 10

Two mu and two delta opiopeptides were administered intracisternally and morphine was administered systemically to rats. The level of dopamine (DA) and its catabolites, homovanillic acid, dihydroxyphenylacetic acid and 3-methoxytramine were measured by high-pressure liquid chromatography with electrical detector in rat striatum to determine: 1) whether opioids alter the release of DA from striatal neuron (which would be indicated by changes in the level of 3-methoxytramine, the extraneuronal catabolite) and 2) whether delta or mu ligands have a greater effect on DA turnover. We found that the levels of 3-methoxytramine did not rise in response to the administration of any opiopeptide or morphine. However, mu opiopeptides produced a small but significant decrease in these levels, indicating that there was no increase, but instead a slight decrease in DA release. The delta opiopeptides produced larger increases in homovanillic acid and dihydroxyphenylacetic acid than the mu ligands, indicating that delta ligands are more effective on an equidose basis in increasing the turnover of striatal DA. The opiopeptides were also tested for pharmacological activity at the same dose (3 micrograms/rat). All four peptides were effective in reducing locomotor activity and producing analgesia. One peptide, Tyr-d-Ala-Gly-N-Mephe-Met-O-ol, also produced catalepsy. There was no segregation of these two behavioral responses according to ligand specificity. Morphine acted like a delta ligand in affecting DA turnover.
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PMID:Effects of delta and mu opiopeptides on the turnover and release of dopamine in rat striatum. 609 4

Electric shock (ES) produces an opiate-like analgesia and catalepsy in rats, which may be mediated by endogenous opioid systems. The present study was designed to investigate the alterations of endogenous opioid receptors by an intermittent ES application. In a case of opiate agonists, [3H]dihydromorphine and [3H]D-Ala-Met-enkephalinamide, the application of ES produced a decrease of [3H]ligands' binding capacity. On the contrary, the binding capacity of the opiate antagonist [3H]naloxone was increased by the ES application. These results suggest that endogenous putative opioid agonist- and antagonist-type receptors are differently regulated in vivo.
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PMID:Different changes by acute electric footshock of opioid agonist and antagonist receptors in rat brain. 609 6

In the spinal cord of the barbiturate anaesthetized cat, D-phenylalanine (DPA) depressed spontaneous and amino acid-induced firing of multireceptive dorsal horn neurones. The excitation of these neurones by noxious and non-noxious cutaneous stimuli was non-selectively depressed by DPA. DPA did not potentiate the depressant action of methionine enkephalin on these cells. Although naloxone reduced the depressant action of DPA, this was associated with increases in spontaneous firing. Spinal reflexes in this preparation are tonically inhibited by opioid peptides. Intravenous DPA (20-70 mg/kg) did not potentiate this inhibition but produced small increases in spinal reflexes. Collectively these data do not support the hypothesis that analgesia from DPA results from potentiation of endogenously released methionine enkephalin.
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PMID:Lack of interaction between methionine enkephalin and D-phenylalanine on nociceptive and non-nociceptive responses of dorsal horn neurones of the cat. 609 12

1 The interaction of naloxone with various anaesthetics was studied both in vivo and in vitro.2 Naloxone (10 mg/kg) did not significantly alter the anaesthetic duration of halothane, diethylether, ketamine, pentobarbitone or Althesin.3 Naloxone (10 mg/kg) reduced the analgesic activity of nitrous oxide, ketamine and morphine in the rat tail-flick test. With the exception of pentobarbitone and Althesin, the other anaesthetic agents also induced analgesia but were not antagonized by naloxone.4 Specific [(3)H]-dihydromorphine binding was displaced by the opiates naloxone (IC(50) = 7.6 nm), methionine-enkephalin (Met-enkephalin, IC(50) = 40 nm) and morphine (IC(50) = 54 nm). Similarly, displacement was observed with xylazine (IC(50) = 9 mum), ketamine (IC(50) = 130 mum) and Althesin (IC(50) = 150 mum); other anaesthetics agents tested were inactive in mm concentrations.5 Ketamine (IC(50) = 200 mum) and xylazine (IC(50) = 9.5 mum) were also capable of displacing specific [(3)H]-D-Ala(2)-enkephalin (D-Leu) binding, as were morphine (IC(50) = 95 nm) and Met-enkephalin (IC(50) = 40 nm).6 On the stimulated guinea-pig ileum, Met-enkephalin and morphine inhibited the contractions, the IC(50) values were 30 nm and 50 nm respectively. The anaesthetics ketamine (IC(50) = 10 mum) and Althesin (IC(50) = 8 mum) were active. Xylazine (IC(50) = 12 nm) exhibited considerable potency in inhibiting the contractions on this preparation. Naloxone 0.5 mum produced a 1000 fold shift in the opiate dose-response curve but the anaesthetic responses showed only slight sensitivity to antagonism by naloxone.7 The activity of Althesin was found to be due to the vehicle in which this anaesthetic is solubilised.8 Whilst several anaesthetic agents showed analgesic activity, specific dihydromorphine binding displacement or guinea pig ileum inhibiting activity, these effects showed variable sensitivity to naloxone.
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PMID:Opiate-like analgesic activity in general anaesthetics. 611 17

1 The actions of the opiate receptor drugs, morphine, methionine-enkephalin (Met-enkephalin) and naloxone were compared with the actions of the alpha 2-receptor drugs, clonidine, xylazine and yohimbine on analgesic tests, in vitro bioassay (guinea-pig ileum and mouse vas deferens), and radioligand displacement studies on rat brain membrane preparations. 2. Both opiate and alpha 2-agonist drugs showed analgesic activity but whilst the alpha 2-agonist analgesic activity was antagonized by only alpha 2-antagonists, the analgesic activity of morphine was antagonized by both naloxone and yohimbine. In the in vitro tests, both groups of agonists inhibited electrically evoked activity; however in these experiments only antagonism of opiates by naloxone and alpha 2-agonists by yohimbine could be shown and it is concluded that in these systems the activity of the alpha 2-agonists is mediated via the presynaptic alpha 2-receptors only. 3 In the radioligand studies the drugs acting at alpha 2-receptors were active in the micromolar range at displacing labelled opioid ligands but opiates did not displace labelled alpha 2-ligands. 4 It is concluded that drugs which act on alpha 2-receptors interfere with the in vivo analgesic effects of opiates and weakly displace opioid radioligand binding, but opioids do not affect alpha 2 agonist analgesia and do not appear to displace alpha 2-agonist radioligand binding.
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PMID:Interactions of drugs active at opiate receptors and drugs active at alpha 2-receptors on various test systems. 612 44

A nociceptive stimulus (e.g., foot pinch) produced a significant increase in firing in cells in the nucleus reticularis gigantocellularis (NRGC) and surrounding areas of the rat brain. Substance P (SP), a putative nociceptive neurotransmitter, infrequently produced an increase in spontaneous neuronal firing when administered micro-iontophoretically to these areas. These data indicate that the NRGC is an area involved in nociception. However, SP does not appear to be the primary nociceptive neurotransmitter or neuromodulator in the NRGC because SP did not mimic or enhance the response to the nociceptive stimulus. Morphine (MS) and methionine-enkephalin (ENK), administered microiontophoretically, rarely had any effect on spontaneous neuronal firing or rarely modified the increase in neuronal firing evoked by the nociceptive stimulus. For this reason, the NRGC is apparently not an area where MS and ENK act directly to produce analgesia.
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PMID:Substance P, morphine and methionine-enkephalin: effects on spontaneous and evoked neuronal firing in the nucleus reticularis gigantocellularis of the rat. 615 55


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