I think the answers to your questions are unfortunately not scientific but business related Fast track designation must be requested by the company developing

I think the answers to your questions are unfortunately not scientific but business related Fast track designation must be requested by the company developing the drug. J&j is developing esketamine; I don't know of any companies developing arketamine I think a big reason j&j decided to develop esketamine vs ketamine is because ketamine is an old approved generic drug (i.e. Cheap). they chose it over arketamine probably for all the pharmacologic and therapeutic reasons cited in the second to last paper you link to. Last December they released phase 2 data that looked pretty good though there were dissociate side effects The new data on arketamine are interesting but I view them with a grain of salt. There's only so much you can conclude about depression biology and structure activity relationship from animal models. Plus the mechanism of action of ketamine is so complex and poorly understood that by trying to be too precise with our receptor targeting we risk losing desired traits. We don't really know that AMPA is a better target than NMDAR; and we don't know the right ratio, and we don't know whether there are other important receptors beyond these