Disease relevance of Ro 20 1724

• Expression of these cDNAs in Escherichia coli and monkey COS-7 cells demonstrated that the encoded cAMP-PDEs had similar affinities for the cAMP substrate and were equally sensitive to a number of PDE inhibitors (rolipram greater than Ro 20-1724 greater than cilostamide) [1].
• Treatment of atopic dermatitis MNL with varying concentrations of the cAMP PDE inhibitor Ro 20-1724 resulted in progressively decreasing amounts of IgE synthesis, statistically significant at the 10(-4) M and 10(-5) M concentrations [2].
• Ro 20-1724 and other cyclic nucleotide-altering agents may have therapeutic potential in the future treatment of psoriasis [3].
• Inhibition of type IV phosphodiesterase by Ro 20-1724 attenuates endotoxin-induced acute renal failure [4].
• Rolipram, Ro 20-1724, and ICI 63-197 (group 1) caused hypothermia, hypoactivity, forepaw shaking, grooming, and head twitches [5].

Psychiatry related information on Ro 20 1724

• The naltrexone stimulus-generalization curve and dose-response curve for loss of body weight were shifted to the left by IBMX and Ro 20-1724, which produce quasi-withdrawal, but not by papaverine, which does not [6].

High impact information on Ro 20 1724

• CGRP, in the presence of the phosphodiesterase inhibitor Ro 20-1724, increased phosphorylation of the alpha and delta subunits of the AChR [7].
• Preliminary incubation of fibroblasts with 8-bromo cGMP or phosphodiesterase inhibitors, including 3-isobutyl-1-methylxanthine, Ro 20-1724, and cilostamide, however, prevented the ANF suppression of cAMP [8].
• The PGE(2)-induced vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE(1) (0.01 to 1 nmol/L) [9].
• Incubation of cultured VSMCs with a PDE4-selective inhibitor, Ro 20-1724, markedly potentiated both the antimigratory effect and the increase in cAMP caused by forskolin [10].
• When 100 microM Ro-20-1724 was applied to the HERG 4M channel, missing all PKA sites, there was no significant shift in the activation curve, and the current amplitude was not reduced [11].

Chemical compound and disease context of Ro 20 1724

• Pretreatment with milrinone or Ro-20-1724 enhanced LPS-induced increases in plasma tumor necrosis factor-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR [12].
• Repeated administration of dexamethasone and Ro 20-1724 with each OvA exposure attenuated all of the chronic inflammatory responses: early and late phase responses, hyperreactivity and eosinophilia [13].

Biological context of Ro 20 1724

• The widely used phosphodiesterase inhibitor MIX (1-methyl 3-isobutyl xanthine) blocked insulin antagonism of cAMP-stimulated glycogenolysis in rat hepatocytes but other phosphodiesterase inhibitors including Ro 20-1724 had no effect [14].
• A calmodulin-stimulated phosphodiesterase activity was inhibited by MIX, 7-BzMIX, 8-MeOMeMIX, and MB 22948 (IC50 values = 1-10 microM) but was not inhibited by IIX and Ro 20-1724 [15].
• Insulin did suppress lipolysis stimulated by Ro 20-1724, an inhibitor of soluble cAMP phosphodiesterase activity [16].
• Selective inhibition of cAMP hydrolysis by Ro 20-1724 and its greater effectiveness in elevating cAMP levels in slices of psoriatic epidermis is one explanation for its clinical superiority in treating psoriatic lesions [17].
• In animals pretreated with endotoxin, Ro 20-1724 attenuated norepinephrine-induced increases in mesenteric vascular resistance (P = .054) and decreases in mesenteric blood flow (P < .01) [18].

Anatomical context of Ro 20 1724

• However, addition of 70 microM Ro 20-1724 to the adherence assay did not potentiate the inhibitory effects of CGS 21680 and NECA on PMA-stimulated neutrophil adherence [19].
• The granulocyte response to the phosphodiesterase inhibitor RO 20-1724 in asthma [20].
• This monocyte fraction accounted for most of the elevated leukocyte-PDE activity and was a cytosolic, cAMP-specific, low Michaelis constant, calcium-calmodulin-dependent enzyme, inhibited by the cAMP-PDE inhibitor, Ro 20-1724 [21].
• The various effects of the phosphodiesterase inhibitor D-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO-20-1724) on fat cell metabolism were examined and compared to those obtained with 1-methyl-3-isobutylxanthine (IBMX) [22].
• We next examined the effect of the phosphodiesterase inhibitor Ro 20-1724 on interleukin-4 production and found a significant reduction in cultures of atopic mononuclear leukocytes [23].

Associations of Ro 20 1724 with other chemical compounds

• FMLP-mediated adhesion was inhibited by a diverse group of cAMP modulators: forskolin, isoproterenol, phosphodiesterase IV inhibitors (rolipram and Ro 20-1724), but not phosphodiesterase III inhibitors (milrinone and bemoradan) [24].
• The influence of two selective phosphodiesterase 4 (PDE4) inhibitors, rolipram and Ro 20-1724, on the induction of BDNF mRNA by antidepressant treatment was examined [25].
• Papaverine and Ro 20-1724 inhibit cyclic nucleotide phosphodiesterase activity and increase cyclic AMP levels in psoriatic epidermis in vitro [17].
• However in the presence of the non-methylxanthine phosphodiesterase inhibitor, Ro-20-1724, both adenosine and NECA elicit a reversible increase in intracellular cAMP concentration [26].
• However, the cholinergic agonist delays the induction of TH elicited by either RO 20-1724 or PGE1 [27].

Gene context of Ro 20 1724

• The PDE4 inhibitors rolipram and Ro 20-1724 both increase renin secretion in rabbits and also enhance the renin response to beta-adrenergic stimulation [28].
• By utilizing either cilostamide, a PDE3-selective inhibitor, or Ro 20-1724, a PDE4-selective inhibitor, PDE3 and PDE4 activities were shown to account for 15% and 55% of total VSMC cyclic AMP phosphodiesterase (PDE) activity [29].
• 4. Activation of CFTR by xanthines was not mimicked by the calcium ionophore A23187, adenosine, UTP, ATP or the specific phosphodiesterase inhibitors rolipram, Ro 20-1724 and milrinone [30].
• These results suggest that cyclic AMP (cAMP)-elevating agents (PGE2, FK, RO 20-1724) down-regulate the capacity of adherent neutrophils to mount the respiratory burst in response to TNF [31].
• RESULTS: When used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-alpha, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice [32].

Analytical, diagnostic and therapeutic context of Ro 20 1724

• In addition, microinjection of the selective PDE III inhibitor Ro 20-1724 into the rat brain stem has been shown to produce analgesia.(ABSTRACT TRUNCATED AT 400 WORDS)[33]
• Ro 20-1724: an agent that significantly improves psoriatic lesions in double-blind clinical trials [3].
• Two double-blind studies comparing the effectiveness of the cyclic nucleotide-altering agent (4-[3-butoxy-4-methoxybenzyl]-2-imidazolidinone) (Ro 20-1724) vs vehicle have demonstrated that this compound can improve psoriatic lesions [3].
• Bronchoalveolar lavage after repeated OvA exposures revealed eosinophilia which was attenuated by Ro 20-1724 and dexamethasone [13].
• Fifteen rats were anesthetized, instrumented and administered a constant rate intravenous infusion of either Ro 20-1724 (10 micrograms/kg/min; n = 6) or vehicle (n = 9) [4].

References