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)

Enkephalins are a biochemical pathway for endogenous analgesia. A number of compounds inhibit degradation of enkephalins within the body. One of these compounds, D-phenylalanine (DPA), has been shown to increase the pain threshold in animals. It is hypothesized that this naloxone reversible analgesia is induced by DPA blockage of enkephalin degradation by the enzyme carboxypeptidase A. Preliminary studies of chronic pain patients have shown a response rate to DPA from 32% to 75%. This study was a double-blind crossover evaluation of a randomized parallel design to determine the efficacy of DPA in 30 subjects with chronic pain from varied etiology which was unrelieved by multiple therapeutic interventions. Each patient received a stabilized therapeutic regimen during this study consisting of four weeks of either DPA 250 mg or lactose (placebo) orally four times a day. After four weeks the DPA and placebo groups were crossed over for an additional four weeks of treatment. Pain was quantified using a visual analog pain scale and a cold pressor test. Data from the pain questionnaires revealed more pain relief on DPA reported by 25% of the patients, more pain relief on placebo reported by 22% of the patients, and no difference in pain relief reported by 53% of the patients. Lowest pain level of the visual analog scale was reported by 47% of the patients on DPA and 53% on placebo. There appears to be no significant analgesic effect from D-phenylalanine in chronic pain patients when compared to placebo.
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PMID:Analgesic effectiveness of D-phenylalanine in chronic pain patients. 352 9

The effect of D-Phenylalanine (D-Phe), putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in incubation mixture (up to 10(-3) mol/l) the hydrolysis of exogenous 3H-Met5-and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that that pharmacological activity of D-Phe is not directly related to the endogenous opiate system.
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PMID:The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome. 376 85

It had previously been shown that D-phenylalanine and hydrocinnamic acid, two in vitro inhibitors of carboxypeptidase A, possess an analgesic action when injected i.p. in mice. We have studied the in vivo effects of indole-3-acetic acid, another carboxypeptidase A inhibitor, and of the following analogs of D-phenylalanine substituted in position 4: D-tyrosine, p-fluoro-D-phenylalanine and trifluoroacetyl-p-fluoro-D-phenylalanine. Whereas indole-3-acetic acid caused a higher and shorter analgesia in comparison with D-phenylalanine, p-fluoro-D-phenylalanine and its N-trifluoroacetyl derivative yielded both a greater and a much longer lasting analgesic effect. Since the latter compound showed only slight inhibitory activity on carboxypeptidase A in vitro, we suggest that inhibition of this enzyme and analgesia might not be directly correlated.
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PMID:Antinociceptive effect of some carboxypeptidase A inhibitors in comparison with D-phenylalanine. 407 40

The recently discovered native endomorphins play an important role in opioid analgesia, but their metabolic fate in the organism remains relatively little known. This paper describes the application of high-performance liquid chromatography combined with electrospray ionization mass spectrometry to identify the degradation products resulting from the incubation of endomorphins with proteolytic enzymes. The native endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2 (1), and endomorphin-2, H-Tyr-Pro-Phe-Phe-NH2 (2), and an analog of endomorphin-2, H-Tyr-Pro-Phe-Phe-OH (3), were synthetized, and the levels of their resistance against carboxypeptidase A, carboxypeptidase Y, aminopeptidase M and proteinase A were determined. The patterns of peptide metabolites identified by this method indicated that carboxypeptidase Y first hydrolyzes the C-terminal amide group to a carboxy group, and then splits the peptides at the Trp3-Phe4 or Phe3-Phe4 bond. The remaining fragment peptides are stable against the enzymes investigated. Carboxypeptidase A degrades only analog 3 at the Phe3-Phe4 bond. Aminopeptidase M cleaves the peptides at the Pro2-Trp3 or Pro2-Phe3 bond. The C-terminal fragments hydrolyze further, giving amino acids and Phe-NH2-s while the N-terminal part displays a resistance to further aminopeptidase M digestion. Proteinase A exhibits a similar effect to carboxypeptidase Y: the C-terminal amide group is first converted to a carboxy group, and one amino acid is then split off from the C-terminal side.
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PMID:Liquid chromatographic study of the enzymatic degradation of endomorphins, with identification by electrospray ionization mass spectrometry. 1042 May 97