Psychoanalytic sociology and the traumas of history: Alexander Mitscherlich between the disciplines

This article examines the way aspects of recent history were excluded in key studies emerging from psychoanalytic social psychology of the mid-twentieth century. It draws on work by Erikson, Marcuse and Fromm, but focuses in particular on Alexander Mitscherlich. Mitscherlich, a social psychologist associated with the later Frankfurt school, was also the most important psychoanalytic figure in postwar Germany. This makes his work significant for tracing ways in which historical experience of the war and Nazism was filtered out of psychosocial narratives in this period, in favour of more structural analyses of the dynamics of social authority. Mitscherlich?s 1967 work The Inability to Mourn, co-authored with Margarete Mitscherlich, is often cited as the point at which the ?missing? historical experience flooded back into psychoanalytic accounts of society. I argue that this landmark publication doesn?t hail the shift towards the psychoanalysis of historical experience with which it is often associated. These more sociological writers of the mid-century were writing before the impact of several trends occurring in the 1980s-90s which decisively shifted psychoanalytic attention away from the investigation of social authority and towards a focus on historical trauma. Ultimately this is also a narrative about the transformations which occur when psychoanalysis moves across disciplines

A high-throughput electrophysiology assay identifies inhibitors of the inwardly rectifying potassium channel Kir7.1

Kir7.1 is an inwardly rectifying potassium channel that has been implicated in controlling the resting membrane potential of the myometrium. Abnormal uterine activity in pregnancy plays an important role in postpartum hemorrhage, and novel therapies for this condition may lie in manipulation of membrane potential. This work presents an assay development and screening strategy for identifying novel inhibitors of Kir7.1. A cell-based automated patch-clamp electrophysiology assay was developed using the IonWorks Quattro (Molecular Devices, Sunnyvale, CA) system, and the iterative optimization is described. In total, 7087 compounds were tested, with a hit rate (>40% inhibition) of 3.09%. During screening, average Z' values of 0.63 ± 0.09 were observed. After chemistry triage, lead compounds were resynthesized and activity confirmed by IC50 determinations. The most potent compound identified (MRT00200769) gave rise to an IC50 of 1.3 µM at Kir7.1. Compounds were assessed for selectivity using the inwardly rectifying potassium channel Kir1.1 (ROMK) and hERG (human Ether-à-go-go Related Gene). Pharmacological characterization of known Kir7.1 inhibitors was also carried out and analogues of VU590 tested to assess selectivity at Kir7.1

A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate and antagonize activation of P2X1 receptors.

Analogues of the P2 receptor antagonists pyridoxal-5'-phosphate and the 6-azophenyl-2',4'-disulfonate derivative (PPADS), in which the phosphate group was cyclized by esterification to a CH2OH group at the 4-position, were synthesized. The cyclic pyridoxine-alpha4, 5-monophosphate, compound 2 (MRS 2219), was found to be a selective potentiator of ATP-evoked responses at rat P2X1 receptors with an EC50 value of 5.9 +/- 1.8 microM, while the corresponding 6-azophenyl-2',5'-disulfonate derivative, compound 3 (MRS 2220), was a selective antagonist. The potency of compound 3 at the recombinant P2X1 receptor (IC50 10.2 +/- 2.6 microM) was lower than PPADS (IC50 98.5 +/- 5.5 nM) or iso-PPADS (IC50 42.5 +/- 17.5 nM), although unlike PPADS its effect was reversible with washout and surmountable. Compound 3 showed weak antagonistic activity at the rat P2X3 receptor (IC50 58.3 +/- 0.1 microM), while at recombinant rat P2X2 and P2X4 receptors no enhancing or antagonistic properties were evident. Compounds 2 and 3 were found to be inactive as either agonists or antagonists at the phospholipase C-coupled P2Y1 receptor of turkey erythrocytes, at recombinant human P2Y2 and P2Y4 receptors, and at recombinant rat P2Y6 receptors. Similarly, compounds 2 and 3 did not have measurable affinity at adenosine A1, A2A, or A3 receptors. The lack of an aldehyde group in these derivatives indicates that Schiff's base formation with the P2X1 receptor is not necessarily required for recognition of pyridoxal phosphate derivatives. Thus, compounds 2 and 3 are relatively selective pharmacological probes of P2X1 receptors, filling a long-standing need in the P2 receptor field, and are also important lead compounds for future studies