A1: As opposed to biochemical, which is often the case for drugs that were "reverse engineered." Reverse engineered means Pharma/biotech/academic lab started with a single drug target molecule, usually a protein, that was compellingly associated with a disease; then they isolated potent chemical matter (i.e., clinical drugs) that modulated the function of said protein; finally, they figured out how to dose it safely in human patients. Problem is many clinical drugs fail during trials because they are ineffective, exposing a fatal flaw in the original oversimplification of going all in on one drug target for a complex disease.

A2: Normal eukaryotic cells have intact secretory pathways that allow them to manufacture cellular material and then transport these products from one internal location to another, or from inside the cell to outside the cell, the process called secretion. By contrast, the red blood cell is a highly specialized cell type - basically a giant sac of hemoglobin and cytoskeletal matrix. In the process of becoming this sac, the internal compartments, or organelles, were lost.

A3: Internal/intracellular membranes. Everyone forgets that our cells are like Babushka dolls, with smaller sealed compartments inside the outermost "skin" of the cell, which is a membrane, too. Also, don't forget that membranes are bilayers! (Please see this excellent Wikipedia summary for what I mean by a bilayer: http://en.wikipedia.org/w...)

A4: Yes.

A5: Ionization leads to high solubility in the water or aqueous phase, i.e., not IN membranes. Think of a vinaigrette. Ionized molecules of sertraline have a net charge, in this case positive (i.e., an extra proton), and so will reside in the vinegar phase. On the other hand, the unionized form of sertraline/Zoloft is uncharged, and, because it is sufficiently hydrophobic, will reside in the oil phase.

A6: The neurotrophic/neurogenic hypothesis may be more grounded in membrane biology than we currently appreciate.