Pinacidil Monohydrate is a guanidine that opens potassium channels producing direct peripheral vasodilatation of arterioles. It has been used as a vasodilator drug to treat hypertension.
Pinacidil Monohydrate is a guanidine that opens potassium channels producing direct peripheral vasodilatation of arterioles. It has been used as a vasodilator drug to treat hypertension.
Apart from the above-mentioned application Pinacidil Monohydrate has also been gaining recognition in the field of stem cell research. Pinacidil has been successfully used in enhancing survival of stem cells. Human embryonic stem cells (hESCs) can be maintained as undifferentiated stem cells in vitro and induced to differentiate into a variety of somatic cell types. Therefore, hESCs are an excellent source of differentiated cell types that can be used to replace diseased cells of a tissue. But it is eminent to maintain effective cell banks and therefore efficient cryopreservation of hESCs is important. However, conventional slow freezing methods usually lead to low rates of recovery after thawing cells and their replating in culture.
Pinacidil Monohydrate has shown to promote survival of hESCs after cryopreservation. A study conducted using different cell lines have shown the cells to exhibit normal hESC morphology, retain normal karyotype, and express characteristic hESC markers (OCT4, SSEA3, SSEA4 and TRA-1-60). Moreover, the cells retained the capacity to differentiate into derivatives of all three embryonic germ layers as demonstrated by differentiation through embryoid body formation. Thus, the use of pinacidil offers an efficient method for recovery of cryopreserved dissociated human ES cells.
Pinacidil increases cell numbers by promoting survival or attachment of hESCs at the time of plating. It also prevents apoptosis of disassociated hESCs and does not affect the differentiation and pluripotency of the hESCs.
This drug works primarily by influencing mitochondrial membrane ATP channels to stay open when the cell is under oxidative stress, allowing for more potassium molecules to enter the mitochondria while simultaneously preventing dangerous depolarization of the membrane. The influx of potassium prevents the release of the pro-apoptotic complex cytochrome c, effectively blocking the activation of programmed cell death that is ubiquitous in stem cell transplants.
Pinacidil has been approved by FDA for clinical use and has been suggested to be more useful in commercial applications.
References:
Novel regulators of stem cell fates identified by a multivariate phenotype screen of small compounds on human embryonic stem cell colonies - IvanaBarbaric, Paul J.Gokhale, MarkJones , AdamGlen, DuncanBake, Peter W.Andrews
Bioprocessing of Cryopreservation for Large-Scale Banking of Human Pluripotent Stem Cells - Yan Li and Teng Ma
The mode of action of pinacidil and its analogs P1060 and P1368: results of studies in rat blood vessels Weston AH, Southerton JS, Bray KM, Newgreen DT, Taylor SG.