Model experiments of otoconia stability after canalith repositioning procedure of BPPV.

CONCLUSION: Postural restrictions are probably not necessary after the canalith repositioning procedure (CRP). OBJECTIVES: Epley reported the effect of CRP for benign paroxysmal positional vertigo (BPPV). After CRP, patients are often requested to restrict postural change. However, some studies suggested that CRP may work without postural restrictions. The present study aimed to determine the necessity of post-maneuver postural restriction using the frog labyrinth model. METHODS: The otoconial mass from the sacculus was placed on the utricular macular otoconia, mimicking a condition after CRP. The stability of the otoconial mass was observed by tilting the preparation, immediately, 3 min, and 5 min after it was placed on the macular otoconia. The utricular macula was maintained in the vertical plane for 10 s, during which period the behavior of the otoconial mass was observed. In experiment 1 the utricular macula was intact, in experiment 2 otoconia were partially removed, and in experiment 3 they were totally removed from the macula. RESULTS: In experiments 1 and 2, in all preparations the otoconial mass became stabilized after 3 min. Even in experiment 3, in most preparations the otoconial mass became stabilized after 5 min.

Is subnanomolar binding affinity required for the in vivo imaging of acetylcholinesterase? Studies on 18F-labeled G379.

Acetylcholinesterase (AChE) is an important cholinergic marker of Alzheimer's disease (AD) and shows reduced activity in postmortem AD brain tissues. 1-(4-Fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-fluoro-2-yl)methyl]piperidine (G379, ), an AChE inhibitor with a subnanomolar IC(50) (0.56 nM), was prepared as a (18)F-labeled radioligand ([(18)F]) and evaluated in mice. Metabolism studies of [(18)F] showed no metabolites in the mouse brain. Tissue distribution studies demonstrated its uniform regional distribution in the mouse brain, suggesting that this radioligand is not suitable for the in vivo imaging of AChE. This result along with reports on radiolabeled N-benzylpiperidine lactam benzisoxazole (IC(50) < 1 nM) and other radiolabeled benzylpiperidine derivatives (IC(50) > 1 nM) suggested that a subnanomolar IC(50) may not be the only important factor in determining the suitability of a radioligand for in vivo studies of AChE.

Discovery of novel neuronal voltage-dependent calcium channel blockers based on emopamil left hand as a bioactive template.

A series of novel neuronal voltage-dependent calcium channel (VDCC) blockers, with inhibitory activity at low micromolar and moderate solubility in water, was discovered by constructing and screening a focused library based on emopamil (1) left hand (ELH) as a bioactive template.

Practical synthesis of chiral emopamil left hand as a bioactive motif.

An asymmetric synthesis of (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile (emopamil left hand, 2) has been completed by use of the MAD (methyl aluminum bis(4-methyl-2,6-di-tert-butylphenoxide)-induced rearrangement of a chiral epoxyalcohol as the key reaction. The stereochemistry of the chiral quaternary center was confirmed by transformation of 2 to (S)-noremopamil. This method requires minimal purification procedures and affords high chemical and optical yields. Acid-catalyzed isomerization of an allylaldehyde and retro-aldol type racemization at the quaternary carbon of a nitrile-alcohol were encountered.