Pyrrolifene

Pyrrolidone derivatives

The pyrrolidone (2-oxopyrrolidine) family of chemicals has been the subject of research for more than three decades. Experimental and clinical work first focused on their so-called nootropic effects; later came the possibilities for neuroprotection after stroke and use as antiepileptic agents. Piracetam, the first of the class, was developed by pioneering research by C Giurgea in the late 1960s, and it was he who coined the term "nootropic", to mean enhancement of learning and memory. The term is sometimes extended to include other actions such as neuroprotection. These properties, together with the lack of other generally adverse psychopharmacological actions (eg, sedation, analgesia, or motor or behavioural changes), distinguish the pyrrolidones from other psychoactive drug classes. The mechanisms of action of these drugs are still not fully established; indeed, different compounds in this class may have different modes of action. Interest in this drug class has recently been reawakened by the licensing of levetiracetam as a potentially major new antiepileptic drug and of piracetam for its antimyoclonic action and effects after stroke and in mild cognitive impairment. Other drugs in this class are currently at an advanced stage of development, and the renewal of interest in this therapeutic area is likely to mean not only that more pyrrolidones will enter clinical practice in the next few years but also that the clinical indications of drugs already licensed will widen.

Workplace environmental exposure level guide: n-Methyl-2-pyrrolidone

n-Methyl-2-pyrrolidone (NMP) is a widely used solvent with a mild amine-like odor that can exist in a vapor or aerosol at moderate temperatures. In humans, NMP was reported to induce weak and transient eye irritation and headache. NMP was not a dermal sensitizer and has a low acute toxicity via oral, dermal, and inhalation routes. NMP was not genotoxic/mutagenic in a battery of in vitro and in vivo studies. Furthermore, NMP was not carcinogenic in rats although species-specific liver tumors were identified in mice. Chronic studies in the rat provided a NOAEL of 10 ppm (40 mg/m³) causing only minor effects in males (slightly reduced mean body weight) at 100 ppm (400 mg/m³). Developmental toxicity was considered the critical endpoint (decreased fetal body weights at non-maternally toxic doses). Benchmark dose and PBPK models were utilized to derive an internal dose of 350-470 mg·h/L as a NOAEL for this response and a human equivalent air concentration of 350-490 ppm. With the application of adjustment factors, an 8-h time-weighted average WEEL value of 15 ppm (60 mg/m³) was derived and is expected to provide a significant margin of safety against any potential adverse health effects in workers. To address the potential for respiratory irritation, a short-term exposure level of 30 ppm (120 mg/m³) was derived, and a skin notation is assigned because of the contribution of dermal absorption to the systemic toxicity of NMP.

Effect of N-2-methyl-pyrrolidone on Enterococcus faecalis biofilms

This study aimed to investigate the effect of N-2-methyl-pyrrolidone (NMP) on the removal of Enterococcus faecalis biofilm. Colony-forming unit (CFU) counting, crystal violet staining, and extracellular DNA (eDNA) measurements were performed to analyze removal of the biofilms formed in a bovine root canal. A confocal laser scanning microscope (CLSM) assay was used to measure the volume of the biofilms. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to investigate the biofilm-associated genes. The morphologic feature of the biofilms was observed under a scanning electron microscope (SEM). NMP decreased CFU numbers, eDNA levels, and biofilm biomass significantly compared to control. qRT-PCR showed that NMP increased the expression of some virulence-associated genes, but downregulated genes related to colonization and persistency. SEM showed that the numerous dentinal tubules were exposed as a result of removal of the biofilm. Collectively, NMP has the potential to be used as a vehicle for endodontic intracanal medicaments.

Formalin-free soft embalming of human cadavers using N-vinyl-2-pyrrolidone: perspectives for cadaver surgical training and medical device development

The traditional apprenticeship approach to surgical skill education for young surgeons has drastically changed to more systematic surgical training using cadavers. Cadavers fixed with formalin are not suitable for surgical training because of their associated health hazards and overhardening. Recently, we established a formalin-free soft preservation method for human cadavers using N-vinyl-2-pyrrolidone. Since 2012, 61 cadavers have been embalmed with pyrrolidone in our institution. Tissues of pyrrolidone-embalmed cadavers are soft and pliable, and their bodies can be preserved for as long as 37 months without any signs of corruption. In this review, we introduce our recent attempts to apply pyrrolidone-embalmed cadavers in surgical and medical procedure training, including endotracheal intubation, motion physiology of the vocal folds, laparoscopic surgery, endoscopic skull base surgery, and development of novel medical devices. Future research perspectives on pyrrolidone embalming are discussed.

N-vinyl-2-pyrrolidone and polyvinyl pyrrolidone