UV Spectrophotometric Method for Quantification of Rivastigmine Tartrate in Simulated Nasal Fluid: Development and Validation

Background: Rivastigmine Tartrate belongs to the class of cholinesterase inhibitors in Anti-alzheimer’s disease with optimum therapeutic efficacy. Till now no validated method of its quantification has been reported in simulated nasal fluid. Objective: The current research investigation aims to develop a rapid, simple, and reliable UV spectrophotometric method for the quantitative determination of the pure form of Rivastigmine Tartrate in SNF. Method: A suitable method was developed by using double beam UV spectrophotometer and selection of a suitable solvent system for estimation of Rivastigmine Tartrate at absorbance maxima 263nm in SNF. The method was validated for various parameters like including accuracy, linearity and precision as per the International Conference on Harmonization guidelines. Results: The method developed by selecting simulated nasal fluid as the solvent system satisfied the optimum condition of the good quality peak at the selected wavelength. The results proposed the developed method for Rivastigmine Tartrate quantification in the simulated nasal fluid to be linear in the working concentration range of 5-60 µg/ml with a co-relation coefficient of 0.998. The % accuracy was found to be 99.8 -100.57. The % RSD values were < 2 while LOD & LOQ values were detected to be 0.316 and 1.053 respectively. Conclusion: The stated method was analyzed to be rapid, accurate, reliable, and precise. Further, it can be used in checking the quality control parameters of the Rivastigmine Tartrate in routine analysis.

Cholinesterase Inhibitors Used for the Management of Alzheimer’s Disease: A Review

Alzheimer’s disease (AD) is defined as a progressive neurodegenerative disorder that has lately become the top reason for dementia in the elderly population (usually above 60-65 years). As mentioned before, most AD cases are sporadic and have a late onset. This disease is characterized by impairment of higher cognitive functions like deficits in memory, language comprehension, coordination, etc. The primary pathophysiology behind Alzheimer’s disease is loss of cholinergic innervation due to the formation of neuritic (senile) amyloid-beta plaques and tau protein-containing neurofibrillary tangles (NFTs) in parts of the brain associated with memory functions. These neurofibrillary tangles (NFTs) and amyloid β plaques can cause the induction of other aetiologies of Alzhedisease-likes like neuroinflammation and central hyperexcitability. The brain's main regions affected by Alzheimer’s disease are the neocortex, the basal nucleus of Meynert, and the hippocampus. These areas are associated with higher cognitive functions like memory, arousal, attention, sensory processing, etc. Thus, cholinesterase inhibitors have been widely used as first-line drug therapy for symptomatic relief in Alzheimer’s disease. They function by inhibiting acetylcholinesterase or catabolizing it and henceforth enhancing synaptic availability of Acetylcholine. The commonly prescribed drugs of this class include donepezil, galantamine, physostigmine, metrifonate, and rivastigmine. This article will discuss the widely used cholinesterase inhibitors (old & new) for managing AD symptoms in detail.

Using Virtual AChE Homology Screening to Identify Small Molecules With the Ability to Inhibit Marine Biofouling

The search for effective yet environmentally friendly strategies to prevent marine biofouling is hampered by the large taxonomic diversity amongst fouling organisms and a lack of well-defined conserved molecular targets. The acetylcholinesterase enzyme catalyses the breakdown of the neurotransmitter acetylcholine, and several natural antifouling allelochemicals have been reported to display acetylcholinesterase inhibitory activity. Our study is focussed on establishing if acetylcholinesterase can be used as a well-defined molecular target to accelerate discovery and development of novel antifoulants via sequential high-throughput in silico screening, in vitro enzymatic studies of identified compound libraries, and in vivo assessment of the most promising lead compounds. Using this approach, we identified potent cholinesterase inhibitors with inhibitory concentrations down to 3 μM from a 10,000 compound library. The most potent inhibitors were screened against five microfouling marine bacteria and marine microalgae and the macrofouling tunicate Ciona savignyi. No activity was seen against the microfoulers but a potent novel inhibitor of tunicate settlement and metamorphosis was discovered. Although only one of the identified active cholinesterase inhibitors displayed antifouling activity suggesting the link between cholinesterase inhibition and antifouling is limited to certain compound classes, the study highlights how in silico screening employed regularly for drug discovery can also facilitate discovery of antifouling leads.