Diisoprop­yl{2-[2-(2-oxopyrrolidin-1-yl)acetamido]eth­yl}ammonium hydrogen sulfate

The structure of the title compound, C14H28N3O2 +·HSO4 −, a nootropic drug (pramiracetam) investigated for cognition-enhancing properties, is closely similar to that of the previously determined acetonitrile solvate, both structures being characterized by the presence of ribbons of hydrogen-bonded ions. The pyrrolidine ring adopts an envelope conformation

Involvement of K channels and calcium-independent mechanisms in hydrogen sulfide-induced relaxation of rat mesenteric small arteries.

Endogenous hydrogen sulfide (H2S) is involved in the regulation of vascular tone. We hypothesized that lowering of calcium and opening of K channels as well as calcium-independent mechanisms are involved in H2S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H2S] after addition to closed tubes of NaSH, Na2S, and GYY4137 were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H2S], GYY4137 caused more relaxation in relation to released free [H2S] than NaSH and Na2S in rat mesenteric small arteries. Simultaneous measurements of [H2S] and tension showed that 15 μM of free H2S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaSH lowered calcium and caused relaxation of norepinephrine-contracted arteries, while high extracellular potassium reduced NaSH relaxation without corresponding calcium changes. In norepinephrine-contracted arteries, NaSH (1 mM) lowered phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) remained unchanged. Inhibitors of guanylate cyclase, protein kinase A and G failed to reduce NaSH relaxation, while blockers of voltage-gated KV7 channels inhibited NaSH relaxation, and blockers of mitochondrial complex I and III abolished NaSH relaxation. CONCLUSION: the present findings suggest that low micromolar concentrations of free H2S by a dual mechanism opens K channels followed by lowering of smooth muscle calcium and by a mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation

'Smart drugs': Do they work? Are they ethical? Will they be legal?

Beyond pharmacological approaches to the treatment of memory loss that results from Alzheimer's disease or stroke, there lies a broad diagnostic penumbra of 'age-associated memory impairment'. New research that offers to attain the ancient goal of improving our cognitive ability raises an important issue — the use, by healthy people, of such pharmacological tools as cognitive enhancers. Here, I review the history and effectiveness of such supposed 'nootropics', and the ethical, social and legal issues raised by their potential use in disease and in the enhancement of 'normal' cognition