138 results match your criteria Toxicity Cyclic Antidepressants


Phosphodiesterase 2 inhibitor Hcyb1 reverses corticosterone-induced neurotoxicity and depression-like behavior.

Psychopharmacology (Berl) 2020 Nov 14;237(11):3215-3224. Epub 2020 Sep 14.

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, the State University of New York, Buffalo, NY, 14214, USA.

Rationale: Currently available PDE2 inhibitors have poor brain penetration that limits their therapeutic utility in the treatment of depression. Hcyb1 is a novel selective PDE2 inhibitor that was introduced more lipophilic groups with polar functionality to the scaffold pyrazolopyrimidinone to improve the blood-brain barrier (BBB) penetration. Our previous study suggested that Hcyb1 increased the neuronal cell viability and exhibited antidepressant-like effects, which were parallel to the currently available PDE2 inhibitor Bay 60-7550. Read More

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November 2020

Orange peels modulate antioxidant markers and key enzymes relevant to erection in the penile tissue of paroxetine-treated rats.

Andrologia 2019 Oct 26;51(9):e13371. Epub 2019 Jul 26.

Functional Foods and Nutraceuticals Unit, Biochemistry Department, Federal University of Technology, Akure, Nigeria.

In comparison to other antidepressant drugs, erectile dysfunction (ED) is more pronounced in paroxetine use. On the other hand, orange (Citrus sinensis) peels commonly consumed in various forms are used in folkloric medicine for ED management. Thus, this study evaluated the effect of orange peels infusion on sexual behaviour, nitric oxide (NO) level and some enzymes (arginase, phosphodiesterase-5 [PDE-5], acetylcholinesterase [AChE] and adenosine deaminase [ADA]) in paroxetine-treated rats. Read More

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October 2019

Multitarget-directed cotreatment with cilostazol and aripiprazole for augmented neuroprotection against oxidative stress-induced toxicity in HT22 mouse hippocampal cells.

Eur J Pharmacol 2019 Aug 13;857:172454. Epub 2019 Jun 13.

Department of Pharmacology, School of Medicine, Pusan National University, Gyeongsangnam-do, Republic of Korea; Gene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Gyeongsangnam-do, Republic of Korea. Electronic address:

Cerebrovascular dysfunction is crucially associated with cognitive impairment and a high prevalence of psychotic symptoms in the vascular dementia characterized by oxidative stress and multifactorial neurodegeneration. In this study, the significant decrease in BDNF expression in HT22 cells due to HO (0.25 mM) was little affected by either aripiprazole (1 μM) or cilostazol (1 μM) alone, but significantly increased by cotreatment with both drugs. Read More

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Adeno-associated virus-mediated over-expression of CREB-regulated transcription coactivator 1 in the hippocampal dentate gyrus ameliorates lipopolysaccharide-induced depression-like behaviour in mice.

J Neurochem 2019 04 5;149(1):111-125. Epub 2019 Mar 5.

Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang, PR China.

Depression is a highly complex global disabling psychiatric disorder. Unfortunately, the currently available antidepressants are not effective in a significant percentage of patients. Therefore, the underlying mechanisms of depression must be explored at the molecular level to discover new candidate molecular targets for depression treatment. Read More

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Fluoxetine reverses brain radiation and temozolomide-induced anxiety and spatial learning and memory defect in mice.

J Neurophysiol 2019 01 5;121(1):298-305. Epub 2018 Dec 5.

Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Radiation therapy and concomitant temozolomide chemotherapy are commonly used in treatment of brain tumors, but they may also result in behavioral impairments such as anxiety and cognitive deficit. The present study sought to investigate the effect of fluoxetine on the behavioral impairments caused by radiation and temozolomide treatment. C57BL/6J mice were subjected to a single cranial radiation followed by 6-wk cyclic temozolomide administration and were then treated with chronic administration of fluoxetine. Read More

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January 2019

Standardized Citrus unshiu peel extract ameliorates dexamethasone-induced neurotoxicity and depressive-like behaviors in mice.

Metab Brain Dis 2018 12 18;33(6):1877-1886. Epub 2018 Sep 18.

Research group of Functional Food Materials, Research Division of Food Functionality, Korea Food Research Institute (KFRI), 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, 55365, Republic of Korea.

Dried Citrus unshiu peel, also known as Chinpi, have been commonly used as a traditional medicine to improve for allergy, inflammation and hepatopathy. Many previously studies have reported that citrus flavonoids show neuroprotective activities. However, the antidepressant-related effects of C. Read More

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December 2018

Methylene Blue Analogues with Marginal Monoamine Oxidase Inhibition Retain Antidepressant-like Activity.

ACS Chem Neurosci 2018 12 25;9(12):2917-2928. Epub 2018 Jul 25.

Pharmaceutical Chemistry, School of Pharmacy , North-West University , Private Bag X6001 , Potchefstroom 2520 , South Africa.

Methylene blue (MB) possesses diverse medical applications. Among these, MB presents with antidepressant-like effects in animals and has shown promise in clinical trials for the treatment of mood disorders. As an antidepressant, MB may act via various mechanisms which include modulation of the nitric oxide cyclic guanosine monophosphate (NO-cGMP) cascade, enhancement of mitochondrial respiration and antioxidant effects. Read More

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December 2018

Efficient Intracellular Delivery of Cell-Impermeable Cargo Molecules by Peptides Containing Tryptophan and Histidine.

Molecules 2018 06 26;23(7). Epub 2018 Jun 26.

Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA.

We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. Read More

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The neuroprotective and antidepressant-like effects of Hcyb1, a novel selective PDE2 inhibitor.

CNS Neurosci Ther 2018 07 27;24(7):652-660. Epub 2018 Apr 27.

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA.

Aims: Depression is currently the most common mood disorder. Regulation of intracellular cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) signaling by phosphodiesterase (PDE) inhibition has been paid much attention for treatment of depression. This study aimed to investigate the neuroprotective effects of Hcyb1, a novel PDE2 inhibitor, in HT-22 cells and antidepressant-like effects in mouse models of depression. Read More

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Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy.

Neuropharmacology 2018 03 12;131:403-413. Epub 2018 Jan 12.

Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Read More

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Effects of the antidepressant, mianserin, on early development of fish embryos at low environmentally relevant concentrations.

Ecotoxicol Environ Saf 2018 Apr 19;150:144-151. Epub 2017 Dec 19.

Shanghai Applied Radiation Institute, Shanghai University, Shanghai 200444, China. Electronic address:

Pharmaceuticals have been considered as emerging organic contaminants in the environment that might pose huge risk to the non-target aquatic organisms. Mianserin, a tetracyclic antidepressant, is present at low detectable concentrations in the aquatic environment; however, limited attention has been devoted to its potential adverse effects on the aquatic animals. In the present study, we first performed an acute toxicity test for mianserin exposure using zebrafish (Danio rerio) embryos during 4-124h post fertilization (hpf). Read More

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Reduction of cancer cell viability by synergistic combination of photodynamic treatment with the inhibition of the Id protein family.

J Photochem Photobiol B 2018 Jan 5;178:521-529. Epub 2017 Dec 5.

Department of Molecular Biology, University of Salzburg, Billrothstrasse 11, 5020 Salzburg, Austria. Electronic address:

The inhibitor of DNA binding and cell differentiation (Id) proteins are dominant negative regulators of the helix-loop-helix transcription factor family and play a key role during development as well as in vascular disorders and cancer. In fact, impairing the Id-protein activity in cancer cells reduces cell growth and even chemoresistance. Recently, we have shown that a synthetic Id-protein ligand (1Y) consisting of a cyclic nonapeptide can reduce the viability of the two breast cancer cell lines MCF-7 and T47D and of the bladder cancer cells T24 to about 50% at concentrations ≥100μM. Read More

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January 2018

Venlafaxine Attenuates the Development of Morphine Tolerance and Dependence: Role of L-Arginine/Nitric Oxide/cGMP Pathway.

Endocr Metab Immune Disord Drug Targets 2018 ;18(4):362-370

Department of Pharmacology, School of Pharmacy, Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Severe pain reduces quality of life of patients with various diseases, often because chronic morphine therapy results in reduced analgesic effectiveness, or tolerance, leading to escalating doses and distressing adverse effects. Nitric oxide (NO) plays a role in morphine tolerance and dependence.

Objective: Venlafaxine, an antidepressant, is known to modulate nitric oxide (NO) pathway in nervous tissues. Read More

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October 2018

Atrazine suppresses FSH-induced steroidogenesis and LH-dependent expression of ovulatory genes through PDE-cAMP signaling pathway in human cumulus granulosa cells.

Mol Cell Endocrinol 2018 02 30;461:79-88. Epub 2017 Aug 30.

Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Serbia.

Atrazine (ATR) alters female reproductive functions in different animal species. Here, we analyzed whether ATR disturbs steroidogenic and ovulatory processes in hormone-stimulated human cumulus granulosa cells and mechanism of its action. Results showed that treatment of human cumulus granulosa cells with 20 μM ATR for 48 h resulted in lower FSH-stimulated estradiol and progesterone production. Read More

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February 2018

The resolution of acute inflammation induced by cyclic AMP is dependent on annexin A1.

J Biol Chem 2017 08 27;292(33):13758-13773. Epub 2017 Jun 27.

From the Programa de Pós-Graduação em Biologia Celular, Departamento de Morfologia, Instituto de Ciências Biológicas,

Annexin A1 (AnxA1) is a glucocorticoid-regulated protein known for its anti-inflammatory and pro-resolving effects. We have shown previously that the cAMP-enhancing compounds rolipram (ROL; a PDE4 inhibitor) and BtcAMP (a cAMP mimetic) drive caspase-dependent resolution of neutrophilic inflammation. In this follow-up study, we investigated whether AnxA1 could be involved in the pro-resolving properties of these compounds using a model of LPS-induced inflammation in BALB/c mice. Read More

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Rapid Access to Oxazine Fused Furocoumarins and in vivo and in silico Studies of theirs Biological Activity.

Med Chem 2017 ;13(7):625-632

Laboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, P.O. Box: 630090, Novosibirsk. Russian Federation.

Background: The synthesis of 1,2-oxazine-fused linear furocoumarins was performed involving the transition metal catalysis reaction of plant coumarin oreoselone derivatives.

Objective And Method: The Pd-catalyzed desulfonative cross-coupling reactions of 2-(tosyl)oreoselone with terminal alkynes and the successive treatment of the obtained 2-(arylethynyl)furocoumarins with an excess of hydroxylamine gave the expected (Z,E)-3-(hydroxyimino)-2-(arylethynyl)furocoumarins with an (Z:E) ratio of about 1:0.5. Read More

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December 2017

Assessment of the Neuroprotective Effects of Arginine-Rich Protamine Peptides, Poly-Arginine Peptides (R12-Cyclic, R22) and Arginine-Tryptophan-Containing Peptides Following In Vitro Excitotoxicity and/or Permanent Middle Cerebral Artery Occlusion in Rats.

Neuromolecular Med 2017 Sep 18;19(2-3):271-285. Epub 2017 May 18.

Perron Institute for Neurological and Translational Science, QEII Medical Centre, 8 Verdun St, Nedlands, WA, 6009, Australia.

We have demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties with arginine content and peptide positive charge being particularly critical for neuroprotective efficacy. In addition, the presence of other amino acids within arginine-rich peptides, as well as chemical modifications, peptide length and cell-penetrating properties also influence the level of neuroprotection. Against this background, we have examined the neuroprotective efficacy of arginine-rich protamine peptides, a cyclic (R12-c) poly-arginine peptide and a R22 poly-arginine peptide, as well as arginine peptides containing tryptophan or other amino acids (phenylalanine, tyrosine, glycine or leucine) in in vitro glutamic acid excitotoxicity and in vivo rat permanent middle cerebral artery occlusion models of stroke. Read More

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September 2017

Involvement of Akt/GSK3β/CREB signaling pathway on chronic omethoate induced depressive-like behavior and improvement effects of combined lithium chloride and astaxanthin treatment.

Neurosci Lett 2017 05 30;649:55-61. Epub 2017 Mar 30.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address:

Chronic organophosphorus pesticides (OP) exposure is associated with an increased risk of depression, and there is an urgent need to find an effective treatment for the depressive-like symptoms caused by OP. The main purpose of this study was to investigate whether combined lithium chloride (LiCl) and astaxanthin (AST) treatment would manifest synergetic antidepressant effects on mice with chronic OP exposure, and to determine the role of the Akt/GSK3β/CREB signaling pathway. Our results showed that chronic omethoate exposure significantly increased immobility time in behavioral tests and induced neuron damage in HE staining. Read More

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Galanin contributes to monoaminergic dysfunction and to dependent neurobehavioral comorbidities of epilepsy.

Exp Neurol 2017 03 22;289:64-72. Epub 2016 Dec 22.

Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Children's Discovery and Innovation Institute, UCLA, Los Angeles, CA, USA. Electronic address:

Status epilepticus (SE) in rats, along with chronic epilepsy, leads to the development of behavioral impairments resembling depressive disorder and/or attention deficit/hyperactivity disorder (ADHD), thus reflecting respective comorbidities in epilepsy patients. Suppressed neurotransmitter tone in the raphe nucleus (RN)-prefrontal cortex (PFC) serotonergic pathway and in the locus coeruleus (LC)-PFC noradrenergic pathway underlies depressive- and impulsive-like behavioral deficits respectively. We examined possible mechanisms leading to the monoamine dysfunction in brainstem efferents, namely modulatory effects of the neuropeptide galanin on serotonin (5-HT) and norepinephrine (NE) signaling. Read More

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Efficacy of phosphodiesterase-4 inhibitors in juvenile Batten disease (CLN3).

Ann Neurol 2016 12 23;80(6):909-923. Epub 2016 Nov 23.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE.

Objective: Juvenile neuronal ceroid lipofuscinosis (JNCL), or juvenile Batten disease, is a pediatric lysosomal storage disease caused by autosomal recessive mutations in CLN3, typified by blindness, seizures, progressive cognitive and motor decline, and premature death. Currently, there is no treatment for JNCL that slows disease progression, which highlights the need to explore novel strategies to extend the survival and quality of life of afflicted children. Cyclic adenosine monophosphate (cAMP) is a second messenger with pleiotropic effects, including regulating neuroinflammation and neuronal survival. Read More

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December 2016

LPA1 Mediates Antidepressant-Induced ERK1/2 Signaling and Protection from Oxidative Stress in Glial Cells.

J Pharmacol Exp Ther 2016 Nov 7;359(2):340-353. Epub 2016 Sep 7.

Laboratory of Cellular and Molecular Pharmacology, Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy (M.C.O., S.D., P.O.)

Antidepressants have been shown to affect glial cell functions and intracellular signaling through mechanisms that are still not completely understood. In the present study, we provide evidence that in glial cells the lysophosphatidic acid (LPA) receptor LPA mediates antidepressant-induced growth factor receptor transactivation, ERK1/2 signaling, and protection from oxidative stress. Thus, in C6 glioma cells and rat cortical astrocytes, ERK1/2 activation induced by either amitriptyline or mianserin was antagonized by Ki16425 and VPC 12249 (S), which block LPA and LPA receptors, and by AM966, which selectively blocks LPA Cell depletion of LPA with siRNA treatment markedly reduced antidepressant- and LPA-induced ERK1/2 phosphorylation. Read More

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November 2016

Discovery of N-Alkyl Catecholamides as Selective Phosphodiesterase-4 Inhibitors with Anti-neuroinflammation Potential Exhibiting Antidepressant-like Effects at Non-emetic Doses.

ACS Chem Neurosci 2017 01 13;8(1):135-146. Epub 2016 Oct 13.

Department of Neuropharmacology and Novel Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University , Guangzhou 510515, China.

Depression involving neuroinflammation is one of the most common disabling and life-threatening psychiatric disorders. Phosphodiesterase 4 (PDE4) inhibitors produce potent antidepressant-like and cognition-enhancing effects. However, their clinical utility is limited by their major side effect of emesis. Read More

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January 2017

Improvement of daptomycin production via increased resistance to decanoic acid in Streptomyces roseosporus.

J Biosci Bioeng 2016 Oct 29;122(4):427-33. Epub 2016 Jul 29.

Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin 449728, South Korea. Electronic address:

Daptomycin, a cyclic anionic lipopeptide compound produced by Streptomyces roseosporus, is used to treat skin infections caused by multi-drug resistant gram-positive pathogens. The biosynthesis of daptomycin is initiated by the condensation of decanoic acid (DA, a 10-carbon unit fatty acid) and the N-terminal l-tryptophan. So, the addition of DA to the fermentation medium is essential for increasing daptomycin production. Read More

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October 2016

Involvement of PI3K/Akt/FoxO3a and PKA/CREB Signaling Pathways in the Protective Effect of Fluoxetine Against Corticosterone-Induced Cytotoxicity in PC12 Cells.

J Mol Neurosci 2016 Aug 13;59(4):567-78. Epub 2016 Jul 13.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.

The selective serotonin reuptake inhibitor fluoxetine is neuroprotective in several brain injury models. It is commonly used to treat major depressive disorder and related conditions, but its mechanism of action remains incompletely understood. Activation of the phosphatidylinositol-3-kinase/protein kinase B/forkhead box O3a (PI3K/Akt/FoxO3a) and protein kinase A/cAMP-response element binding protein (PKA/CREB) signaling pathways has been strongly implicated in the pathogenesis of depression and might be the downstream target of fluoxetine. Read More

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Desipramine improves depression-like behavior and working memory by up-regulating p-CREB in Alzheimer's disease associated mice.

J Integr Neurosci 2016 Jun 23;15(2):247-60. Epub 2016 Jun 23.

† Department of Physiology, Shanxi Medical University, Taiyuan, China.

Aggregation of amyloid [Formula: see text] protein (A[Formula: see text] and progressive loss of memory are the main characteristics of Alzheimer's disease (AD). It is noteworthy that approximately 40% of AD patients have depressive symptom. The close correlation between cognitive deficits and mental depression suggests a possibility that antidepression treatment might be beneficial to cognitive improvement in AD. Read More

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Antidepressant-like Effects of ZBH2012001, a Novel Potent Serotonin and Norepinephrine Reuptake Inhibitor.

CNS Neurosci Ther 2016 08 20;22(8):700-6. Epub 2016 May 20.

Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

Aims: The present study was conducted to evaluate the antidepressant-like effects of ZBH2012001, a novel potential serotonin and norepinephrine reuptake inhibitor (SNRI).

Methods: Competitive binding assays, calcium flow, and cAMP detection methods were used to determine the affinity of ZBH2012001 for serotonin transporters (SERTs) and norepinephrine transporters (NETs), as well as its selectivity over dopamine transporters (DATs) and 16 other G-protein-coupled receptors (GPCRs) or iron channels. The antidepressant-like effects of ZBH2012001 were determined using the tail suspension test, forced swim test, and learned helplessness paradigm. Read More

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Antidepressant therapies inhibit inflammation and microglial M1-polarization.

Pharmacol Ther 2016 07 18;163:82-93. Epub 2016 Apr 18.

Neuroscience Research, NIBR, Fabrikstrasse 22-3.001.02, Basel 4002, Switzerland.

Macrophages and their counterparts in the central nervous system, the microglia, detect and subsequently clear microbial pathogens and injured tissue. These phagocytic cells alter and adapt their phenotype depending on their prime activity, i.e. Read More

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Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl.

Inorg Chem 2015 Dec 19;54(23):11557-62. Epub 2015 Nov 19.

Université Grenoble Alpes , INAC-SCIB, F-38000 Grenoble, France.

Cyclic peptides with two phosphoserines and two glutamic acids were developed to mimic high-affinity binding sites for uranyl found in proteins such as osteopontin, which is believed to be a privileged target of this ion in vivo. These peptides adopt a β-sheet structure that allows the coordination of the latter amino acid side chains in the equatorial plane of the dioxo uranyl cation. Complementary spectroscopic and analytical methods revealed that these cyclic peptides are efficient uranyl chelating peptides with a large contribution from the phosphorylated residues. Read More

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December 2015

Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

Behav Neurosci 2015 Dec 26;129(6):701-8. Epub 2015 Oct 26.

Department of Physiology and Pharmacology, Karolinska Institutet.

Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). Read More

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December 2015

The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on Chemotherapy-Induced Neuropathic Pain in Rats.

Anesth Analg 2015 Sep;121(3):822-8

From the *Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas; †Department of Anesthesiology, Perioperative Medicine, and Pain Management, University of Miami, LM Miller School of Medicine, Miami, Florida; and ‡Department of Biostatistics, Florida International University, Miami, Florida.

Background: Chemotherapy-induced neuropathic pain is a significant side effect of chemotherapeutic agents. Currently, there are no effective analgesics for chemotherapy-induced neuropathic pain. Rolipram is a selective phosphodiesterase 4 inhibitor, which increases intracellular cyclic AMP in nerve and immune cells. Read More

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September 2015