piperidines and clemizole

Persistent neural activity has been observed in vivo during working memory tasks, and supports short-term (up to tens of seconds) retention of information. While synaptic and intrinsic cellular mechanisms of persistent firing have been proposed, underlying cellular mechanisms are not yet fully understood. In vitro experiments have shown that individual neurons in the hippocampus and other working memory related areas support persistent firing through intrinsic cellular mechanisms that involve the transient receptor potential canonical (TRPC) channels. Recent behavioral studies demonstrating the involvement of TRPC channels on working memory make the hypothesis that TRPC driven persistent firing supports working memory a very attractive one. However, this view has been challenged by recent findings that persistent firing in vitro is unchanged in TRPC knock out (KO) mice. To assess the involvement of TRPC channels further, we tested novel and highly specific TRPC channel blockers in cholinergically induced persistent firing in mice CA1 pyramidal cells for the first time. The application of the TRPC4 blocker ML204, TRPC5 blocker clemizole hydrochloride, and TRPC4 and 5 blocker Pico145, all significantly inhibited persistent firing. In addition, intracellular application of TRPC4 and TRPC5 antibodies significantly reduced persistent firing. Taken together these results indicate that TRPC4 and 5 channels support persistent firing in CA1 pyramidal neurons. Finally, we discuss possible scenarios causing these controversial observations on the role of TRPC channels in persistent firing.

Topics: Action Potentials; Animals; Antibodies; Benzimidazoles; CA1 Region, Hippocampal; Cholinergic Agonists; Indoles; Male; Mice; Neurons; Piperidines; Pyramidal Cells; TRPC Cation Channels

The determination of antihistamines based on the measurement of the critical micelle concentration (c.m.c.) of mixed sodium dodecyl sulfate (SDS)-antihistamine aggregates is proposed. The dye Coomassie Brilliant Blue G (CBBG) was used as a photometric probe for the rapid determination of c.m.c.s. The micellar properties of these drugs permitted the determination of diphenhydramine, antazoline, tripelennamine, diphenylpyraline and clemizole at the micron level with detection limits ranging between 0.1 and 0.7 microns. Hence the proposed method surpassed existing alternative photometric methods used routinely in the quality control of these drugs in sensitivity and featured similar detection limits to fluorimetric methods. The relative standard deviation for 6 micron diphenhydramine was 3.7%. The method was applied to the determination of these drugs in pharmaceutical preparations (solutions, capsules, creams and pills). which were analyzed directly after dissolution of the samples in distilled water.

Topics: Antazoline; Benzimidazoles; Diphenhydramine; Histamine H1 Antagonists; Micelles; Pharmaceutical Preparations; Piperidines; Spectrophotometry; Titrimetry; Tripelennamine