China
Africa
Explore chapters and articles related to this topic
Synthesis of Important Chiral Building Blocks for Pharmaceuticals Using Lactobacillus and Rhodococcus Alcohol Dehydrogenases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marion Rauter, Simon Krebs, Gotthard Kunze
Pękala and coworkers studied the reduction of xanthine derivatives with a methyl ketone moiety by isolated L. kefir ADH as well as by biotransformation using L. kefir whole cells (Pękala et al., 2007; Pękala and Zelaszczyk, 2009). The water soluble substrates pentoxifylline and propentofylline (2.5 mM) were successfully converted to the corresponding secondary (R)-alcohols using the free enzyme with an ee >99% and yields of 96 and 98% with 8% isopropanol for cofactor regeneration. Whole cell L. kefir biotransformation of the substrates gave similar yields with lower costs due to enzyme purification and addition of cofactor not being required, but ee decreased to 98% and 96%. Thus, highly enantiopure substances for pharmacokinetic and pharmacodynamic studies should be produced using free enzymes.
Pharmacologic agents directed at the treatment of pain associated with maladaptive neuronal plasticity
Published in Expert Opinion on Pharmacotherapy, 2022
Joseph V. Pergolizzi, Giustino Varrassi, Peter Magnusson, Frank Breve, Robert B. Raffa, Paul J. Christo, Maninder Chopra, Antonella Paladini, Jo Ann LeQuang, Kailyn Mitchell, Flaminia Coluzzi
Pentoxyfylline and propentofylline are both nonselective phosphodiesterase inhibitors that suppress microglial and astrocyte activity [63]. They may also reduce pro-inflammatory cytokines [49]. Pentoxyfylline is a nonspecific cytokine inhibitor and a phosphodiesterase inhibitor and can inhibit the synthesis of TNF-α, IL-1β, and IL-6 [97,98]. It is a methylxanthine which modulates glial activation and serves as an anti-inflammatory agent shown in a murine study to have anti-hyperalgesic and morphine-sparing effects. It may also partially restore opioid analgesia [99]. Propentofylline is likewise a methylxanthine derivative and a glial modifying drug that may be able to reverse neuropathic pain by microglial inhibition even six weeks following neural injury [100]. Propentofylline has been evaluated for cognitive function with weak evidence in its support [101].
Treatment of central sensitization in patients with chronic pain: time for change?
Published in Expert Opinion on Pharmacotherapy, 2019
Jo Nijs, Laurence Leysen, Johan Vanlauwe, Tine Logghe, Kelly Ickmans, Andrea Polli, Anneleen Malfliet, Iris Coppieters, Eva Huysmans
As explained, increased glial activity may also contribute to CS in patients having chronic pain [40,118]. Targeting glia cells might therefore be an innovative treatment option. Glial inhibitors, including propentofylline, potentially have a desensitizing effect and have been tested for the treatment of neuropathic pain [119]. Unfortunately, human microglia were less responsive to propentofylline treatment [119], casting doubt whether direct microglial inhibition is a relevant therapeutic target for patients with chronic pain [120]. Other pharmacological treatments like minocycline, an antibiotic, theoretically also hold the capacity to target aberrant glial activity in patients with CS, an idea supported by animal work [121–123]. A small randomized clinical trial has shown that a brief treatment with minocycline was associated with a small, but statistically significant reduction in pain in patients with lumbar radiculopathy [124], but data examining whether minocycline reduces pain by inhibiting microglia and decreasing CS in humans are currently unavailable. Taken together, direct pharmacological targeting of glial activation in patients having chronic pain and CS is becoming yet another fruitless attempt to find a biomedical solution for a multimodal and complex biopsychological problem.
Propentofylline reduces mechanical allodynia and induces mitogen-activated protein kinase phosphatase-1: An experimental study in a rat model of acute incisional pain
Published in Neurological Research, 2019
Yuanyuan Yang, Yisa Shi, Juan Jia, Shenghong Wang, Hong Chang, Mingguo Li, Xu Jin, Jing Wang
Mitogen-activated protein kinase phosphatases (MKPs) are a series of protein tyrosine phosphatases [10]. Mechanistically, they bind to the KIM sequence in MAPKs leading to their specific de-phosphorylation [11]. MKP-1, also known as DUSP-1 (dual specificity protein phosphatase 1), is one member of the MKP family which preferentially dephosphorylates p38 MAPK [12]. Several reports have shown that MKP-1 can regulate inflammatory responses [13] and chronic neuropathic pain [14] by specifically dephosphorylating p38. However, its role in regulating acute pain remains to be determined. Propentofylline (PPF) is a biologically active xanthine derivative. Rodent experiments have shown when combined with opioids PPF can be used to treat opioid tolerance [15], enhance their analgesic effect, and reduce the occurrence of adverse reactions. There are also some reports showing that PPF can ameliorate chronic pain, with a possible mechanism related to the inhibition of the activation of microglia and astrocytes [16,17]. Our previous studies have shown that PPF relieves acute incisional pain in rats by inhibiting microglia, astrocytes, and the MAPK JNK signaling pathway [18–20]. Matthew et al. have reported that PPF attenuates both persistent behavioral hypersensitivity and the over-expression of p-p38 [21], and that MKP-1 is the natural negative regulator of p38 [12]. On this basis, we hypothesized that PPF would relieve acute pain by increasing MKP-1 levels leading to a decrease in p-p38 levels.