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Stress induces reinstatement of extinguished cocaine conditioned place preference by a sequential signaling via neuropeptide S, orexin, and endocannabinoid

Chou YH, Hor CC, Lee MT, Lee HJ, Guerrini R, Calo G, et al.

Addict Biol, 2020 Oct 19.
PMID: 33078457 DOI: 10.1111/adb.12971

Neurons containing neuropeptide S (NPS) and orexins are activated during stress. Previously, we reported that orexins released during stress, via orexin OX1 receptors (OX1 Rs), contribute to the reinstatement of cocaine seeking through endocannabinoid/CB1 receptor (CB1 R)-mediated dopaminergic disinhibition in the ventral tegmental area (VTA). Here, we further demonstrated that NPS released during stress is an up-stream activator of this orexin-endocannabinoid cascade in the VTA, leading to the reinstatement of cocaine seeking. Mice were trained to acquire cocaine conditioned place preference (CPP) by context-pairing cocaine injections followed by the extinction training with context-pairing saline injections. Interestingly, the extinguished cocaine CPP in mice was significantly reinstated by intracerebroventricular injection (i.c.v.) of NPS (1 nmol) in a manner prevented by intraperitoneal injection (i.p.) of SHA68 (50 mg/kg), an NPS receptor antagonist. This NPS-induced cocaine reinstatement was prevented by either i.p. or intra-VTA microinjection (i.vta.) of SB-334867 (15 mg/kg, i.p. or 15 nmol, i.vta.) and AM 251 (1.1 mg/kg, i.p. or 30 nmol, i.vta.), antagonists of OX1 Rs and CB1 Rs, respectively. Besides, NPS (1 nmol, i.c.v.) increased the number of c-Fos-containing orexin neurons in the lateral hypothalamus (LH) and increased orexin-A level in the VTA. The latter effect was blocked by SHA68. Furthermore, a 30-min restraint stress in mice reinstated extinguished cocaine CPP and was prevented by SHA68. These results suggest that NPS is released upon stress and subsequently activates LH orexin neurons to release orexins in the VTA. The released orexins then reinstate extinguished cocaine CPP via an OX1 R- and endocannabinoid-CB1 R-mediated signaling in the VTA.

Matched MeSH terms: Piperidines
Field efficacy of four insect repellent products against vector mosquitoes in a tropical environment

Yap HH, Jahangir K, Zairi J

J Am Mosq Control Assoc, 2000 Sep;16(3):241-4.
PMID: 11081653

Four insect repellent products (RPs) (RP 1, Experimental Repellent Lotion [Bayrepel 12%]; RP 2, Experimental Repellent Cream [Bayrepel 5%]; RP 3, Off! Insect Repellent II Aerosol [deet 15%]; and RP 4, Off! Skintastic II Cream [deet 7.5%]) were evaluated simultaneously for their efficacy against vector and nuisance mosquitoes. The aim of this study was to compare the relative efficacy of RPs based on a new repellent compound, Bayrepel (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-1-methylpropylester), with deet (N,N-diethyl-m-toluamide)-based RPs. An 8-h field efficacy of above repellents was evaluated against the day-biting mosquito (Aedes albopictus) and night-biting mosquitoes (Culex quinquefasciatus and Anopheles spp.). Evaluation was carried out by exposing humans with repellent-treated bare limbs to mosquitoes landing and to mosquitoes landing and biting. Repellent product 1 or 2 was applied on the left arm and leg, whereas RP 3 or 4 was applied on the right arm and leg, respectively. Application of these 4 RPs significantly reduced (P < 0.05) the landing and the landing and biting of day-biting and night-biting mosquitoes. All 4 RPs were found to be equally effective (P < 0.05) against Ae. albopictus and Cx. quinquefasciatus. However, for protection against Anopheles spp., RPs 1 and 3 exhibited significantly (P < 0.05) better repellency effect than RPs 2 and 4.

Matched MeSH terms: Piperidines
Fulltext Comparison of cardiovascular responses between remifentanil and fentanyl on laryngoscopy and tracheal intubation in patients undergoing elective surgery

Lai, S.C., Choy, Y.C.

Journal of Surgical Academia, 2014;4(1):20-25.
MyJurnal

This was a prospective, randomized, double-blind study comparing the effect of remifentanil and fentanyl on cardiovascular responses from laryngoscopy and tracheal intubation. Forty-four ASA I or II patients aged between 18-65 yrs scheduled for elective surgery under general anaesthesia, were recruited and randomized into two groups. Each patient in Group R received remifentanil of 0.5 mcg/kg bolus over 30 seconds followed by an infusion of 0.25 mcg/kg/min and each patient in Group F received fentanyl of 2 mcg/kg bolus over 30 seconds followed by an infusion of normal saline. Anaesthesia was then induced with propofol, rocuronium and 2% sevoflurane with 100% oxygen. Cardiovascular changes were recorded every minute for 3 minutes after induction and 5 minutes after tracheal intubation. The heart rate remained stable throughout the induction and intubation period in both groups. None of the patients in the remifentanil group develop bradycardia. Systolic blood pressure (SBP) and mean arterial pressure (MAP) were significantly lower in the fentanyl group at the 3rd minute post-induction and 5th minute post- intubation (p < 0.05). Diastolic blood pressure (DBP) in the fentanyl group was significantly lower at the 2nd and 3rd minute post-induction and 4th and 5th minute post-intubation (p < 0.05). The blood pressure remained stable for the remifentanil group throughout the induction and intubation period. Six patients (27.2%) in the fentanyl group and one patient (4.5%) in the remifentanil group experienced hypertension. Three patients (13.7%) from each group experienced hypotensive episodes. In conclusion, remifentanil 0.5 mcg/kg bolus followed by 0.25 mcg/kg/min infusion resulted in SBP, MAP and DBP remained slightly lower than baseline throughout the whole period but still consider stable, as these changes were not statistically significant.

Matched MeSH terms: Piperidines
Fulltext Alkaloids from Piper Nigrum and Piper Betle

Lim, C.M., Ee, G.C.L., Rahmani, M., Bong, C.F.J.

Pertanika Journal of Science & Technology, 2009;17(1):-.
MyJurnal

An investigation, on the roots of Piper nigrum and the aerial parts of Piper betle, has yielded several alkaloids. The dried root sample of Piper nigrum was extracted using various solvents in increasing polarity. The dried aerial part of Piper betle was extracted using the Soxhlet extraction method. The alkaloids isolated were pellitorine(1), (E)-1-[3’,4’- (Methylenedioxy)cinnamoyl]piperidine(2), piperine(3), piperolactam D(4), cepharadione A(5), and 2,4-tetradecadienoic acid isobutyl amide(6). These compounds were isolated using chromatographic methods, while the elucidation of the structures was carried out using MS, IR and NMR techniques. The xtracts of Piper nigrum and Piper betle were also tested for cytotoxicity activities. This is the first report on E)-1-[3’,4’-(Methylenedioxy)cinnamoyl] piperidine(2) from Piper nigrum as a natural product.

Matched MeSH terms: Piperidines
Report - Synthesis of new antibacterial agents encompassing tosyl, piperidine, propanamide and 1,3,4-oxadiazole functionalities

Sattar A, Aziz-Ur-Rehman -, Abbasi MA, Siddiqui SZ, Rasool S, Ali Shah SA

Pak J Pharm Sci, 2020 Jul;33(4):1697-1705.
PMID: 33583804

A series of propanamide compounds 6a-l was derived by N-substitution reactions, encompassing tosyl, piperidine and 1,3,4-oxadiazole moieties. The intended array of compounds 6a-l was afforded by a series of five steps reaction scheme. 1-Tosylpiperidin-4-carboxylate (1) was synthesized by the reaction of tosyl chloride (a) with ethyl isonipecotate (b) under mild basic conditions. Compound 1 was subjected to nucleophillic substitution by hydrazine to synthesize 1-tosylpiperidin-4-carbohydrazide (2). The compound, 5-(1-tosylpiperidin-4-yl)-1,3,4-oxadiazole-2-thiol (3) was synthesized by intermolecular cyclization of compound 2 by CS2 under strong basic conditions. The target compounds, 6a-l, were finally synthesized from 3 by reacting with different electrophiles, 5a-l, in an aprotic polar solvent with sodium hydride as an activator. The different propanamoyl electrophiles, 5a-l, were synthesized by the reaction of different aromatic and aliphatic amines, 4a-l, with 3-bromopropionyl chloride under mild basic conditions. The structural elucidation was carried out using modern spectroscopic techniques including IR, 1H-NMR and EI-MS. The antibacterial potential of synthesized compounds was assessed against five bacterial strains. Compounds 6a, 6c, 6d, 6e and 6f were found to be potent antibacterial agents.

Matched MeSH terms: Piperidines
Fulltext Anesthesia for massive retrosternal goiter with severe intrathoracic tracheal narrowing: the challenges imposed -A case report-

Tan PC, Esa N

Korean J Anesthesiol, 2012 May;62(5):474-8.
PMID: 22679546 DOI: 10.4097/kjae.2012.62.5.474

Anesthetic management of patients with mediastinal masses remains challenging as acute cardiorespiratory decompensation may follow induction of anesthesia. We describe a 57 year old lady with massive retrosternal goiter and severe intrathoracic tracheal compression who had a total thyroidectomy. Comprehensive contingency plans were an essential prerequisite for successful management of difficult airway, including multidisciplinary involvement of otorhinolaryngologic and cardiothoracic surgeons preparing for rigid bronchoscopy and cardiopulmonary bypass. Awake oral fiberoptic intubation was performed under dexmedetomidine sedation. Severe tracheal narrowing necessitated usage of a 5.0 mm uncuffed flexometallic endotracheal tube. Anesthesia was maintained with sevoflurane and dexmedetomidine infusion with target controlled infusion of remifentanil as analgesia. No muscle relaxant was given. Surgical manipulation led to intermittent total tracheal compression and inadequate ventilation. The tumor was successfully removed via the cervical approach. A close working relationship between anesthesiologists and surgeons was the key to the safe use of anesthesia and uneventful recovery of this patient.

Matched MeSH terms: Piperidines
Chrotacumines E and F, two new chromone-alkaloid analogs from Dysoxylum acutangulum (Meliaceae) leaves

Izwan Mohd Lazim M, Safinar Ismail I, Shaari K, Abd Latip J, Ali Al-Mekhlafi N, Morita H

Chem Biodivers, 2013 Sep;10(9):1589-96.
PMID: 24078592 DOI: 10.1002/cbdv.201200391

A chemical investigation of the alkaloidal fraction of Dysoxylum acutangulum leaves led to the isolation and characterization of two new chromone alkaloid analogs named chrotacumines E and F (1 and 2, resp.). Structure elucidation of 1 and 2 was achieved by spectroscopic analyses, including 2D-NMR. Both of these alkaloids exhibited modest activities as tyrosinase inhibitors with 29.2 and 25.8% inhibition at 100 μg/ml, respectively.

Matched MeSH terms: Piperidines/isolation & purification; Piperidines/metabolism; Piperidines/chemistry*
Fulltext Role of bilastine in the management of allergic rhinitis and urticaria: an Asia-Pacific consensus statement

Mösges R, Lee DL, Abong J, Siasoco B, Chow SK, Leong JL, et al.

Asia Pac Allergy, 2016 Jan;6(1):56-66.
PMID: 26844221 DOI: 10.5415/apallergy.2016.6.1.56

The prevalence of allergic diseases is increasing globally, most particularly in middle- to low-income countries. This article examines the burden of allergic rhinitis and chronic urticaria in the Asia-Pacific region, unmet clinical needs, and the potential role of bilastine in the management of these conditions. An International Advisory Group meeting was convened in association with the Asian Pacific Society of Respirology Annual Congress in November 2014, followed by a literature review, and consensus-based outcomes from the meeting and literature review are described. Regional estimates of the prevalence of allergic rhinitis range from 10% to 50%, while little is known regarding the burden of urticaria in the Asia-Pacific region. A survey of allergy patients in the region identified fast, complete, and long-lasting symptom relief as the medication attributes most important to patients. International treatment guidelines for allergic rhinitis and urticaria advocate the first-line use of second-generation, no-sedating H1-antihistamines, such as bilastine, over their first-generation counterparts and a range of these agents are available to Asia-Pacific patients. The newer agents possess many of the properties of an "ideal" antihistamine (once daily administration, rapid and complete symptom relief, limited potential for drug-drug interactions, minimal side effects). The burgeoning prevalence of allergic diseases in the Asia-Pacific region and the uncontrolled symptoms that these patients experience demand a new antihistamine that offers the highest number of positive features according to the international guidelines.

Matched MeSH terms: Piperidines
Effect of piperine on liver function of CF-1 albino mice

Rao PJ, Kolla SD, Elshaari F, Elshaari F, Awamy HE, Elfrady M, et al.

Infect Disord Drug Targets, 2015;15(2):131-4.
PMID: 26205799

BACKGROUND: Piperine is isolated from Piper nigrum popularly known as black pepper. Previous studies have demonstrated the beneficial effects of piperine in various health conditions. Additionally, it is a powerful bioenhancer for many drugs. Piperine extract is believed to potentiate the effect of drugs by several folds. The present study is focused on its individual effect on liver function.
MATERIALS AND METHODS: A total of 30 CF-1 albino mice obtained from the animal house of faculty of Medicine, Benghazi University, Benghazi, Libya were included in the study. These mice were fed with high cholesterol diet and divided into 2 groups. Twenty mice were administered piperine at a dose of 5mg/kg body weight. Piperine was isolated in Department of Pharmacognosy, Faculty of Pharmacy, Benghazi University, Benghazi and 10 mice were not administered piperine but fed with high fat diet. These mice were anesthetized with ketamine and halothane and blood was drawn from each mouse before the study and after three weeks by cardiocentesis. Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase and total protein were measured by authenticated methods.
RESULTS: Serum alanine amino transferase was significantly elevated (p=0.0002) in group A mice after the administration of Piperine extract for three weeks compared to those of group B mice. Serum aspartate amino transferase was elevated significantly (p=0.046) and alkaline phosphatase (p= 0.0001) also was significantly increased after the administration of piperine. Serum total protein (p= 0.011) values were significantly decreased after the use of piperine for three weeks in group A mice.
CONCLUSION: This study showed that there might have been a considerable damage to liver with piperine extract. Further research may be required to prove this damage to liver function.

Matched MeSH terms: Piperidines/isolation & purification; Piperidines/pharmacology*; Piperidines/toxicity*
Synthesis, spectral analysis and biological evaluation of sulfamoyl and 1,3,4-oxadiazole derivatives of 3-pipecoline

Rehman A, Aslam SJ, Abbasi MA, Siddiqui SZ, Rasool S, Shah SAA

Pak J Pharm Sci, 2019 May;32(3):987-996.
PMID: 31278711

Heterocyclic chemistry is an important field of organic chemistry due to therapeutic potential. The minor modification in the structure of poly-functional compounds has great effect on therapeutic ability. In the presented research work, substituted 1,3,4-oxadiazole derivatives, 8a-p, have been synthesized by the reaction of 1-(4-bromomethylbenzenesulfonyl)-3-methylpiperidine (7) and 5-substituted-1,3,4-oxadiazole-2-thiol (4a-p). The 5-substituted-1,3,4-oxadiazole-2-thiol were synthesized by converting carboxylic acids correspondingly into esters, hydrazides and oxadiazoles. Secondly the electrophile, 1-(4-Bromomethylbenzenesulfonyl)-3-methylpiperidine (7), was prepared by the reaction of 3-methylpiperidine with 4-bromomethylbenzenesulfonyl chloride in the presence of water and Na2CO3 under pH of 9-10. The compounds were structurally corroborated through spectroscopic data analysis of IR, EI-MS and 1H-NMR. The screening for antibacterial activity revealed the compounds to be moderate to excellent inhibitors against bacteria under study. Anti-enzymatic activity was assessed against urease enzyme and 1-{[4-({[5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}methyl)phenyl]sulfonyl}-3-methylpiperidine (8d) was the most active one.

Matched MeSH terms: Piperidines/chemistry
BSA Binding, molecular docking and in vitro biological screening of some new 1, 2, 4-triazole heterocycles bearing azinane nucleus

Iqbal J, Rehman A, Abbasi MA, Siddiqui SZ, Khalid H, Laulloo SJ, et al.

Pak J Pharm Sci, 2020 Jan;33(1):149-160.
PMID: 32122843

A series of new compounds (5a-q), derived from 5-(1-(4-nitrophenylsulfonyl) piperidin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were proficiently synthesized to evaluate their biological activities. 1-(4-Nitrophenylsulfonyl) piperidine-4-carbohydrazide (2) was refluxed with phenylisothiocyanate to yield an adduct which was cyclized to compound 3 by reflux reaction with 10 % potassium hydroxide. The targeted compounds 5a-q, were synthesized by stirring alkyl/aralkyl halides (4a-q) and compound 3 in a polar aprotic solvent. 1H-NMR, 13C-NMR, EI-MS and IR spectral techniques were employed to confirm the structures of all the synthesized compounds. The compounds were biologically evaluated for BSA binding studies followed by anti-bacterial, anti-inflammatory and acetylcholinesterase (AChE) activities. The active sites responsible for the best AChE inhibition were identified through molecular docking studies. Compound 5e bearing 4-chlorobenzyl moiety found most active antibacterial and anti-inflammatory agent among the synthesized compounds. The whole library of synthesized compounds except compounds 5d and 5f was found highly active for AChE inhibition and recommended for in vivo studies so that their therapeutic applications may come in utilization.

Matched MeSH terms: Piperidines/chemistry
Assessment of tracheal intubating conditions in children using remifentanil and propofol without muscle relaxant

Batra YK, Al Qattan AR, Ali SS, Qureshi MI, Kuriakose D, Migahed A

Paediatr Anaesth, 2004 Jun;14(6):452-6.
PMID: 15153205

Tracheal intubation in children can be achieved by deep inhalational anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium being widely used despite several side-effects. Studies have shown that oral intubation can be facilitated safely and effectively in children after induction of anaesthesia with propofol and alfentanil without a muscle relaxant. Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is 20-30 times more potent than alfentanil. This clinical study was designed to assess whether combination of propofol and remifentanil could be used without a muscle relaxant to facilitate tracheal intubation in children.

Matched MeSH terms: Piperidines/administration & dosage*
Pisa syndrome secondary to rivastigmine: a case report

Muthupalaniappen L, Rosdinom R, Suguna M

Clin Ter, 2012;163(1):31-2.
PMID: 22362231

Pisa syndrome or pleurothotonus is the persistent flexion of the body and head to one side giving the appearance of the leaning tower of Pisa. It is most commonly caused by typical and atypical antipsychotic drugs. We report a case of Pisa Syndrome caused by prolonged use of high dose cholinesterase inhibitor, rivastigmine. Symptoms subsided when rivastigmine was withdrawn and did not reappear when a different cholinesterase inhibitor, donepezil was introduced. Physicians should be aware of Pisa syndrome and should alert patient of this possibility when starting and stepping up medications. The purpose of reporting this case is to create awareness among general practitioners as it is a reversible condition which responds to removal of the offending drug.

Matched MeSH terms: Piperidines/therapeutic use
Alkaloids from Piper sarmentosum and Piper nigrum

Ee GC, Lim CM, Lim CK, Rahmani M, Shaari K, Bong CF

Nat Prod Res, 2009;23(15):1416-23.
PMID: 19809914 DOI: 10.1080/14786410902757998

Detailed chemical studies on the roots of Piper sarmentosum and Piper nigrum have resulted in several alkaloids. The roots of P. sarmentosum gave a new aromatic compound, 1-nitrosoimino-2,4,5-trimethoxybenzene (1). Piper nigrum roots gave pellitorine (2), (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (3), 2,4-tetradecadienoic acid isobutyl amide (4), piperine (5), sylvamide (6), cepharadione A (7), piperolactam D (8) and paprazine (9). Structural elucidation of these compounds was achieved through NMR and MS techniques. Cytotoxic activity screening of the plant extracts indicated some activity.

Matched MeSH terms: Piperidines/chemistry
Ifenprodil Reduced Expression of Activated Microglia, BDNF and DREAM Proteins in the Spinal Cord Following Formalin Injection During the Early Stage of Painful Diabetic Neuropathy in Rats

Ismail CAN, Suppian R, Ab Aziz CB, Long I

J Mol Neurosci, 2021 Feb;71(2):379-393.
PMID: 32671697 DOI: 10.1007/s12031-020-01661-1

The pharmacological inhibition of glial activation is one of the new approaches for combating neuropathic pain in which the role of glia in the modulation of neuropathic pain has attracted significant interest and attention. Neuron-glial crosstalk is achieved with N-methyl-D-aspartate-2B receptor (NMDAR-2B) activation. This study aims to determine the effect of ifenprodil, a potent noncompetitive NMDAR-2B antagonist, on activated microglia, brain-derived neurotrophic factors (BDNF) and downstream regulatory element antagonist modulator (DREAM) protein expression in the spinal cord of streptozotocin-induced painful diabetic neuropathy (PDN) rats following formalin injection. In this experimentation, 48 Sprague-Dawley male rats were randomly selected and divided into four groups: (n = 12): control, PDN, and ifenprodil-treated PDN rats at 0.5 μg or 1.0 μg for 7 days. Type I diabetes mellitus was then induced by injecting streptozotocin (60 mg/kg, i.p.) into the rats which were then over a 2-week period allowed to progress into the early phase of PDN. Ifenprodil was administered in PDN rats while saline was administered intrathecally in the control group. A formalin test was conducted during the fourth week to induce inflammatory nerve injury, in which the rats were sacrificed at 72 h post-formalin injection. The lumbar enlargement region (L4-L5) of the spinal cord was dissected for immunohistochemistry and western blot analyses. The results demonstrated a significant increase in formalin-induced flinching and licking behavior with an increased spinal expression of activated microglia, BDNF and DREAM proteins. It was also shown that the ifenprodil-treated rats following both doses reduced the extent of their flinching and duration of licking in PDN in a dose-dependent manner. As such, ifenprodil successfully demonstrated inhibition against microglia activation and suppressed the expression of BDNF and DREAM proteins in the spinal cord of PDN rats. In conclusion, ifenprodil may alleviate PDN by suppressing spinal microglia activation, BDNF and DREAM proteins.

Matched MeSH terms: Piperidines/pharmacology; Piperidines/therapeutic use*
Association and correlation of different chemotherapeutic regimens and doses with onset and severity of anemia among solid cancer patients

Hassan BA, Yusoff ZB, Hassali MA, Othman SB

Asian Pac J Cancer Prev, 2011;12(10):2753-8.
PMID: 22320987

INTRODUCTION: Anemia is considered as one of the most frequent hematological demonstration of malignant diseases, which lead to momentous impairment in every tissues and organs of cancer patients and put them under serious stress. This major problem may arise because of the underlining diseases (i.e., cancer diseases) or radiotherapy or chemotherapy treatment received. This present study tries to find the association between anemia onset and severity with different chemotherapeutics regimens used in the treatment of several solid cancers and to find the association of anemia onset and severity with different doses of these chemotherapeutics drugs.
METHODS: This retrospective observational study was conducted in Penang General Hospital on 534 anemic solid cancer patients who were admitted between 2003 and 2009. The main statistical tests used were Chi-square test and Logistic regression test for categorical data. While for continues data the main statistical tests were Linear regression and correlation test. The significance of the result will be when the P<0.05, while the confidence interval for this study was 95%.
RESULTS: FEC, 5-FU+5-FU, Docetaxel and Cisplatin+ 5-FU regimen has strong association and correlation with anemia onset and severity. However the associations and correlations with anemia severity were stronger than those with the onset. Different doses of 5-FU, cyclophosphamide, docetaxel and cisplatin play a critical role in anemia onset and severity.
CONCLUSION: Monitoring and determination of hemoglobin levels for cancer patients treated with FEC, 5-FU+5-FU, Docetaxel, Cisplatin+ 5-FU specifically with high doses must be emphasized and a focus of particular attention.

Matched MeSH terms: Piperidines/adverse effects; Piperidines/therapeutic use
Estrogen receptor (ER)-α, β and progesterone receptor (PR) mediates changes in relaxin receptor (RXFP1 and RXFP2) expression and passive range of motion of rats' knee

Dehghan F, Yusof A, Muniandy S, Salleh N

Environ Toxicol Pharmacol, 2015 Nov;40(3):785-91.
PMID: 26447688 DOI: 10.1016/j.etap.2015.09.004

The high risk of knee injuries in female may be associated with sex-steroid hormone fluctuations during the menstrual cycle by its effect on ligaments and tendons stiffness. This study examined changes in knee range of motion in presence of estrogen and progesterone and investigated the interaction of their antagonists to relaxin receptors.

Matched MeSH terms: Piperidines/administration & dosage; Piperidines/pharmacology
Flavopiridol Inhibits TGF-β-Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2

Rostam MA, Shajimoon A, Kamato D, Mitra P, Piva TJ, Getachew R, et al.

J Pharmacol Exp Ther, 2018 Apr;365(1):156-164.
PMID: 29438988 DOI: 10.1124/jpet.117.244483

Transforming growth factor-β (TGF-β) is a pleiotropic growth factor implicated in the development of atherosclerosis for its role in mediating glycosaminoglycan (GAG) chain hyperelongation on the proteoglycan biglycan, a phenomenon that increases the binding of atherogenic lipoproteins in the vessel wall. Phosphorylation of the transcription factor Smad has emerged as a critical step in the signaling pathways that control the synthesis of biglycan, both the core protein and the GAG chains. We have used flavopiridol, a well-known cyclin-dependent kinase inhibitor, to study the role of linker region phosphorylation in the TGF-β-stimulated synthesis of biglycan. We used radiosulfate incorporation and SDS-PAGE to assess proteoglycan synthesis, real-time polymerase chain reaction to assess gene expression, and chromatin immunoprecipitation to assess the binding of Smads to the promoter region of GAG Synthesizing genes. Flavopiridol blocked TGF-β-stimulated synthesis of mRNA for the GAG synthesizing enzymes, and chondroitin 4-sulfotransferase (C4ST-1), chondroitin sulfate synthase-1 (ChSy-1) and TGF-β-mediated proteoglycans synthesis as well as GAG hyperelongation. Flavopiridol blocked TGF-β-stimulated Smad2 phosphorylation at both the serine triplet and the isolated threonine residue in the linker region. The binding of Smad to the promoter region of the C4ST-1 and ChSy-1 genes was stimulated by TGF-β, and this response was blocked by flavopiridol, demonstrating that linker region phosphorylated Smad can pass to the nucleus and positively regulate transcription. These results demonstrate the validity of the kinases, which phosphorylate the Smad linker region as potential therapeutic target(s) for the development of an agent to prevent atherosclerosis.

Matched MeSH terms: Piperidines/pharmacology*
Development of anti-acanthamoebic approaches

Mungroo MR, Tong T, Khan NA, Anuar TS, Maciver SK, Siddiqui R

Int Microbiol, 2021 Aug;24(3):363-371.
PMID: 33754231 DOI: 10.1007/s10123-021-00171-3

Acanthamoeba keratitis is a sight-endangering eye infection, and causative organism Acanthamoeba presents a significant concern to public health, given escalation of contact lens wearers. Contemporary therapy is burdensome, necessitating prompt diagnosis and aggressive treatment. None of the contact lens disinfectants (local and international) can eradicate Acanthamoeba effectively. Using a range of compounds targeting cellulose, ion channels, and biochemical pathways, we employed bioassay-guided testing to determine their anti-amoebic effects. The results indicated that acarbose, indaziflam, terbuthylazine, glimepiride, inositol, vildagliptin and repaglinide showed anti-amoebic effects. Compounds showed minimal toxicity on human cells. Therefore, effects of the evaluated compounds after conjugation with nanoparticles should certainly be the subject of future studies and will likely lead to promising leads for potential applications.

Matched MeSH terms: Piperidines/pharmacology
Novel Piperine compound AB05 (N-5-(3,4-dimethoxyphenyl) -2E,4E pentadienylpiperidine) inhibits H1N1 influenza virus propagation in vitro

Mohammed A, Velu AB, Al-Hakami AM, Meenakshisundaram B, Esther P, Abdelwahid SA, et al.

Trop Biomed, 2020 Dec 01;37(4):1062-1073.
PMID: 33612758 DOI: 10.47665/tb.37.4.1062

Pandemic H1N1 influenza virus respiratory illness has become an inevitable global health concern. With antigenic drift, it becomes necessary to have drugs over tailor-made HIN1 vaccine every year. In the current study, we screened many Piperine derivative in which, N-5-(3,4-dimethoxyphenyl)-2E,4E-pentadienylpiperidine (AB05) and was further studied for anti-H1N1influenza virus activity and compared with other stains in-vitro on MDCK cell line. Initial cytotoxic doses of AB05 for the MDCK cell line were > 25µM. The results showed a dose-dependent reduction of the viral plaque's in the adsorption assay with EC50 of 0.33 µM. The mechanism of AB05 was by inhibition of matured viral release as evaluated by the time of virus addition with incubation of 6-10 hours. With the promising H1N1 virucidal activity of AB05, we included various strains of human influenza virus to screen AB05 inhibition of Neuraminidase (NA). The result showed 70% NA inhibition in WSN (H1N1), 90% in H3N2 and Influenza B and 49% in Tamiflu resistant H1N1). Further our In silco docking studies substantiated experimental results by showing the difference in binding and cooperation between H1N1 and N3N2. Together these observations illustrate that Piperine derivative AB05 is a promising lead molecule which needs further evaluation in animal models.

Matched MeSH terms: Piperidines/pharmacology*

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