Disease relevance of FK 33-824

• These results show that patients with acromegaly and hyperprolactinemia due to pituitary adenomas and patients with pituitary dwarfism do not respond well to FK 33-824, presumably because of hypothalamic or pituitary derangement [1].
• In patients with acromegaly, there was little or no increase in GH and PRL after FK 33-824 [1].
• Plasma pituitary hormone responses to the synthetic enkephalin analog (FK 33-824) in normal subjects and patients with pituitary diseases [1].
• The effect of D-Ala2, MePhe4, Met-(0)enkephalinol (Sandoz FK 33-824; 0.5 mg, im) on pituitary hormone secretion was studied in 11 patients with Addison's disease and 11 patients with ACTH-dependent Cushing's disease [2].
• In patients with Cushing's syndrome due to an adrenal adenoma or ectopic ACTH secretion, neither hCRH nor FK 33-824 altered hormone concentrations [3].

Psychiatry related information on FK 33-824

• Dose-related effects of the synthetic met-enkephalin analogue FK 33-824 on esophageal motor activity in healthy humans [4].
• Effects of the synthetic enkephalin analogue FK 33-824 on pain threshold and pain tolerance in man [5].
• Ratings performed by the Brief Psychiatric Rating Scale did not show any significant differences between FK 33-824 and the active placebo pentobarbital [6].
• Intraperitoneal injection of FK 33-824 produced apomorphine-like stereotyped behavior in rats [7].
• Acute effects of the synthetic analogue of methionine enkephalin FK 33-824 on depressive symptoms [8].

High impact information on FK 33-824

• Previously, using the Met-enkephalin analogue FK 33-824 (Sandoz), we determined that brain opioid binding sites could be visualized by electron microscopic autoradiography [9].
• Infusion of 1 mg DAMME into water-deprived volunteers produced a diuresis which was attenuated by naloxone; there was no change in water excretion when subjects were hydrated [10].
• DAMME and other substances with opiate-like activity, such as morphine and beta-endorphin, affect carbohydrate metabolism and insulin secretion [11].
• An enkephalin analogue [D-Ala2, MePhe4, Met(o)-ol] enkephalin (DAMME), given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin [12].
• Here, Ghislain Opdenakker and Jo Van Damme propose the REGA-model (Remnant Epitope Generates Autoimmunity) to explain the generation of autoantigens and their interaction with the T-cell receptor complex [13].

Chemical compound and disease context of FK 33-824

• The effects of FK 33-824, a methionine enkephalin analogue, 313, 625, 1250, 2500, and 5000 ng/kg body wt intramuscularly, on esophageal motor activity and cardiovascular and central nervous functions were studied in 8 healthy men [4].
• FK 33-824 decreased plasma cortisol in normal subjects and patients with pituitary disease [1].
• These results indicate that FK 33-824-induced hyperthermia is not mediated by PG, NE and cAMP, but rather that mu receptors are involved in the induction of hyperthermia by FK 33-824 [14].
• Likewise, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to FK 33-824 [14].
• In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied [15].

Biological context of FK 33-824

• Blood pressure following tilt was significantly decreased by DAMME but not influenced by naloxone, the effect being most marked at 3 hours (placebo = 110 +/- 6/78 +/- 7 mm Hg; naloxone = 106 +/- 10/79 +/- 5 mm Hg; DAMME = 96 +/- 16/67 +/- 8 mm Hg (p less than 0.01) [16].
• Heart rates at 3 hours were: placebo = 87 +/- 16 bpm; naloxone = 88 +/- 19 bpm; DAMME = 89 +/- 23 bpm [16].
• 1. The electrophysiological action of the mu-opioid receptor-preferring agonist D-Ala2, MePhe4, Met(O)5-ol-enkephalin (FK 33-824) on synaptic transmission has been studied in area CA3 of organotypic rat hippocampal slice cultures [17].
• We have examined (1) the effects of naloxone and an opiate peptide, FK 33-824, on LH and FSH secretion in immature male and female rats and (2) the influence of sexual maturation on the ability of this peptide to inhibit LH secretion [18].
• The effect of the synthetic enkephalin analogue Sandoz FK33-824 (DAMME) on gastric emptying and the postprandial secretion of upper gastrointestinal and pancreatic hormones was investigated in six healthy subjects [19].

Anatomical context of FK 33-824

• Effects of an enkephalin analogue (DAMME) on insulin release from cultured rat islets of Langerhans [20].
• 3. FK 33-824 (10 nM to 10 microM) reduced the amplitude of monosynaptic inhibitory postsynaptic potentials (IPSPs) that were elicited in pyramidal cells with local stimulation after pharmacological blockade of excitatory amino acid receptors [17].
• The purpose of this study was to investigate the cardiorespiratory effects of the synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin (FK 33-824) after its administration into the anterior hypothalamic area, paraventricular hypothalamic nuclei and third ventricle [21].
• Gamma interferon (IFN-gamma) can be cytolytic for normal mouse fibroblasts isolated from embryonic or adult tissue (R. Dijkmas, B. Decock, H. Heremans, J. Van Damme, and A. Billiau, Lymphokine Res. 8:25-34, 1989) [22].
• 4. The PIP was prolonged by the GABA-uptake blocker nipecotic acid, was reduced by hyperpolarizing interneurons with the opioid agonist FK 33-824, and was abolished by the GABAB-receptor antagonist CGP 35 348 [23].

Associations of FK 33-824 with other chemical compounds

• Inhibition of glucose-stimulated insulin release by trifluoperazine, an inhibitor of calmodulin, was not overcome by DAMME [20].
• In the first study, nine normal subjects received infusions of DAMME (a metenkephalin analog), naloxone, or saline, and blood pressure, heart rate, and plasma norepinephrine concentration were determined supine and following 5 minutes of 70 degrees head-up tilt at intervals for 6 hours [16].
• 9. In the second study, seven normal subjects had blood pressure reduced by incremental infusions of sodium nitroprusside, and the effects of placebo, naloxone, and DAMME on the slope of the heart period/blood pressure relationship investigated [16].
• Blockade of muscarinic cholinergic receptors by atropine (0.5 mg SC) or histaminergic H1 receptors by diphenhydramine (50 mg IV bolus plus 50 mg infusion) completely suppressed the GH release induced by FK 33-824, without significantly altering the PRL rise induced by the peptide [24].
• Phentolamine failed to alter the PRL rise induced by FK 33-824, while combined FK 33-824-metoclopramide administration induced a greater PRL increase than FK 33-824 alone [24].

Gene context of FK 33-824

• Tumor necrosis factor-alpha (TNF-alpha) has been shown to enhance the synthesis of interleukin-6 (IL-6) and collagenase in human omental microvascular endothelial (HOME) cell (Mawatari, M., Kohno, K., Mizoguchi, H., Matsuda, T., Asoh, K., Van Damme, J. V., Welgus, H. G., and Kuwano, M. (1989) J. Immunol. 143, 1619-1627) [25].
• In this study we investigated the effects of the guanyl derivative of DAMME (G-DAMME) on the serum GH response to an analog of GHRH in normal men [26].
• FK 33-824 increased PRL and GH (p less than 0.001) [27].
• NC28 cDNA encodes a new member of the chemokine family, MCP-3, recently purified from MG-63 osteosarcoma cells by Van Damme et al [28].
• FK 33-824 produced a pronounced and concomitant fall in IR-Nt, IR-EP, IR-LPH, and IR-ACTH levels [29].

Analytical, diagnostic and therapeutic context of FK 33-824

• 2. Most experiments were carried out with a synthetic, stable enkephalin analogue (FK 33-824) administered either by perfusion or by local administration (ionophoresis or pressure application from micropipettes) [30].
• Naloxone or FK 33-824 did not modify LHRH-stimulated release of gonadotropins from organ cultures of anterior pituitary obtained from immature rats [18].
• The synthetic enkephalin, FK 33-824 (FK), is less susceptible to metabolic breakdown and produces long-lasting analgesia in animals [5].
• 7. FK 33-824 produced a decrease in the frequency of miniature, action potential-independent, spontaneous inhibitory synaptic currents (mIPSCs) recorded with whole-cell voltage-clamp techniques, but did not change their mean amplitude [17].
• Naloxone, given alone or with FK 33-824, had a small, but significant, stimulatory effect on cortisol from 60-120 min posttreatment compared to the control group [31].

References