Así que, en menos de 10 años, se han autorizado cinco medicamentos para el tratamiento del Alzheimer: tacrina (1993), donepezilo (1996), rivastigmina (1998), galantamina (2000), anticolinesterásicos los tres primeros, potenciador nicotínico el cuarto, todos ellos eficaces y provechosos y memantina (2002), el primer compuesto del grupo de los moduladores de la neurotransmisión glutamatérgica.
Como podemos apreciar la " Tacrina " es uno de los medicamentos historicos en la lucha en retrasar los efectos del Alzheimer , conste que no existe Farmaco hoy en dia que cure el Alzheimer aún , pues bien aqui tenemos un estudio comparativo de la Tacrina con uno de los Farmacos que estan a punto de iniciar la Fase I , concretamente con el NP-0361 de una Biotecnologica Española llamada NeuroPharma :
The most widely used pharmacological approach for Alzheimer's disease (AD) is the enhancement of cholinergic transmission with acetylcholinesterase inhibitors (AChEI). Tacrine (THA) was the first AChEI in the market but it is now hardly ever used because of its hepatotoxicity and gastrointestinal side effects.
NEUROPHARMA is working on the development of new drugs for AD treatment and has synthesised a series of dual AChEI with a very potent inhibition of both the esteric site of the enzyme and the peripheral site involved in the aggregation of b-amyloid. NP0361, which activity is about 2.5 10-11M, reduced both plaque load and soluble Aβ peptides and improved cognitive functions in a transgenic h-APP mice model. Here, we present the experiments performed to explore whether NP0361 might present a better safety profile than THA exploring the cytotoxicity of these two compounds in cell models of hepatic origin.
No significant difference was observed between chronic and acute treatment of rat hepatocytes primary cultures with NP0361 in contrast to THA which induced a time-dependent increase in toxicity at similar concentrations. Moreover, unlike THA, the toxicity of NP0361 would mainly rely upon its metabolism, since no toxicity was observed in the poorly-metabolizing cells HepG2 or RLEC.
Taken together, these studies show that the mechanism of NP0361 toxicity is different to that of THA in similar cell models. A superior margin of security in these test systems confirms the promise that NP0361 is a good candidate for further developement for the treatment of AD.