Galantamine hydrobromide

Using a modified version of the same methods for quantification of acetylcholine, methanol extracts from sterile and field collected tissue (n = 3) were assayed for AchE activity. In brief, 50 μL of extract or buffer (control) were lightly mixed with 100 mU of AchE for 30 s and left to incubate in the dark at room temperature. After 30 min, 100μL of working solution (400μLM Amplex red reagent, 2 U/mL horseradish peroxidase, 0.2 U/mL choline oxidase, 100μLlM Ach) was added to each well, lightly shaken and placed into the same microplate reader, with excitation and emission wavelengths set to between 530–560 and 590 nm respectively. Fluorescence was measured every 5 min until the reaction was complete (1 h). Assay and a positive control were also used, and consisted of either buffer or 10μLMH₂O₂ solution respectively. AchE activity was determined using Michaelis–Menten enzyme kinetics, and enzyme inhibition was determined by the amount of extract required to reduce Vmax by 50 % of the assay control. Galanthamine hydrobromide (Chromadex) was included as a positive control for all experiments.

In the hidden platform experiments, the escape latency of APP/PS1 with normal saline mice was significantly prolonged compared with wild type mice (P < 0.01), indicating that APP/PS1 transgenic mice had significant spatial learning impairment. In contrast, the mice treated with galanthamine hydrobromide alone or with SYat the dose of 10, 30, 100 mg/kg (P < 0.01) shortened the escape latency as compared with the normal saline treated APP/PS1 mice (Fig. 2b). In the probe test (Fig. 2c and d) with the platform removed, the APP/PS1 normal saline group spent less time in the target quadrant where the platform was once placed and had fewer crossing times than wild type group (P < 0.01). However, mice treated with SY (10, 30 mg/kg) spent significantly increased times in the target quadrant as compared to APP/PS1 normal saline group (P < 0.01). Moreover, SY-treated mice (10 mg/kg, 30 mg/kg) markedly increased the number of crossing (P < 0.01). Meanwhile, treatment with galanthamine hydrobromide (3mg/kg) significantly improved the performances in the probe test (P < 0.01). It should be noted that the body weights of mice in all the groups were at the same level during the test, suggesting that SY had no toxicity effect on mice (data are not shown).

Because hypocortisolism has been suggested as a contributing factor to CFS, several pharmacological studies have attempted to increase cortisol levels. Research by Snorrason et al. (1996) found that 70% of CFS patients reported a minimum of 30% improvement when treated with galanthamine hydrobromide,which increases plasma levels of cortisol.Astudy byMcKenzie et al. (1998) found that a dosage of 25–35 mg resulted in only minimal therapeutic improvements while causing substantial adrenal suppression. In contrast, a study by Cleare et al. (1999), which used a lower dose (5 or 10 mg daily of hydrocortisone) led to significant reductions in self-rated fatigue and disability in patients with CFS and there was no compensatory suppression of endogenous cortisol production. More research clearly needs to be conducted in this area in order to better understand which subgroups respond optimally to which treatments. Regardless of the medication, it is important to note that very few pharmacological agents have been well-established as effective (Reid et al., 2000). What may work well for one person may not be tolerated by, or may be ineffective for, another person, reemphasizing the need to study CFS subgroups.