Effects of long-term administration of ambenonium chloride on motor end-plate fine structure and acetylcholine receptor in rat

Ambenonium chloride was administered orally in a dosage of 6 mg/kg/day to rats for 14–360 days.Motor end-plate fine structure and junctional AChR were quantitatively analyzed in red (soleus) and white (EDL) muscle fibers. In treated animals, degeneration and simplification of postsynaptic folds and widening of synaptic clefts were often observed in soleus end-plates, but infrequently in EDL end-plates. On the other hand, the postsynaptic AChR was reduced markedly in both soleus and EDL end-plates. No presynaptic changes were observed.These results show that long-term administration of Anti-ChE agents in myasthenia gravis may have an adverse effect on neuromuscular transmission.     

Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652.

BACKGROUND: Several lines of studies have suggested the involvement of serotonin transporter (5-HTT) in the pathophysiology of mood disorders. The aim of this study was to examine whether 5-HTT binding was altered in patients with mood disorders using positron emission tomography (PET). METHODS: Thirteen antidepressant-naive or -free patients with mood disorders and 21 age-matched healthy control subjects participated in this study. The patients consisted of 7 with major depressive disorder (MDD) and 6 with bipolar disorder (BD). Positron emission tomography scans were performed using a selective ligand for 5-HTT, [11C](+)McN5652. The uptake was quantified in the thalamus and midbrain by graphical method with reference tissue, and binding potential (BP) was used for the index of 5-HTT binding. RESULTS: Binding potential in the thalamus was significantly increased in patients with mood disorders as compared to control subjects, whereas BP in the midbrain did not differ between the groups. Subgroup comparison showed that MDD patients had significantly higher BP in the thalamus compared to control subjects. Binding potential of the thalamus was higher by approximately 22% in the combined patients and 23% in MDD patients relative to control subjects. CONCLUSIONS: These findings may suggest the possibility of altered 5-HTT in patients with mood disorders. Functional abnormality in the thalamus may be involved in the pathophysiology of mood disorders.