We appreciate the interest of H.M. Dodds and L.P. Rivory in our study on the mechanisms related to the acute cholinergic effects of irinotecan (Blandizzi et al., Br. J. Pharmacol., 132: 73 – 84, 2001). However, despite the efforts made to reproduce our experiments on the in vitro acetylcholinesterase (AChE) assay, we note that these authors still fail to propose any convincing explanation accounting for the discrepancy between our data (Blandizzi et al., 2001) and their repeated observations (Dodds & Rivory, 1999). Therefore, it is conceivable that in vitro assays, carried out on purified preparations of AChE extracted from various sources, do not offer sufficient levels of reliability to allow a clear assessment of the putative anti-AChE properties of irinotecan. For instance, while in their letter Dodds and Rivory emphasize the fact that the incubation time of irinotecan with AChE must be kept as close as possible to zero, at a temperature of 25°C, to avoid spontaneous degradation of the drug, Morton et al. (1999) allowed an incubation time of 22 h at 37°C, which is much longer than that adopted in our study (20 min).

Reply to H.M. Dodds and L.P. Rivory (Letter to the Editor)

COLUCCI, ROCCHINA LUCIA;
2001

Abstract

We appreciate the interest of H.M. Dodds and L.P. Rivory in our study on the mechanisms related to the acute cholinergic effects of irinotecan (Blandizzi et al., Br. J. Pharmacol., 132: 73 – 84, 2001). However, despite the efforts made to reproduce our experiments on the in vitro acetylcholinesterase (AChE) assay, we note that these authors still fail to propose any convincing explanation accounting for the discrepancy between our data (Blandizzi et al., 2001) and their repeated observations (Dodds & Rivory, 1999). Therefore, it is conceivable that in vitro assays, carried out on purified preparations of AChE extracted from various sources, do not offer sufficient levels of reliability to allow a clear assessment of the putative anti-AChE properties of irinotecan. For instance, while in their letter Dodds and Rivory emphasize the fact that the incubation time of irinotecan with AChE must be kept as close as possible to zero, at a temperature of 25°C, to avoid spontaneous degradation of the drug, Morton et al. (1999) allowed an incubation time of 22 h at 37°C, which is much longer than that adopted in our study (20 min).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3166253
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