TY - JOUR
T1 - Excitatory and inhibitory effects of second-generation cholinesterase inhibitors on rat gastrointestinal transit
AU - Braida, Daniela
AU - Virag, Walter
AU - Ottonello, Francesco
AU - Sala, Mariaelvina
PY - 2000
Y1 - 2000
N2 - We investigated the influence of increasing oral doses of second generation acetylcholinesterase inhibitors (AChEI) such as tacrine (0.25, 0.5, 1, 2, 3, 4, 10, and 20 mg kg-1), eptastigmine (0.5, 4, 8, 12, 20 and 40 mg kg-1) and E2020 (0.18, 0.25, 0.5, 1, 2, 3, 4 and 10 mg kg-1) on the distance travelled by a charcoal meal administered 30 min after each compound, in comparison with physostigmine (0.5, 1, 2, 4, 8 and 12 mg kg-1). An inverted U regression was observed with a significant parabola between the centimetres travelled and the log of the doses for all AChEI. The maximal stimulating doses (mg kg-1) were 2 for physostigmine, 4 for eptastigmine, 3 for tacrine and E2020, while the inhibitory doses were 12 for physostigmine, 40 for eptastigmine, 20 for tacrine and 10 for E2020. The stimulating and inhibiting effects on gastrointestinal propulsion were significantly reversed by 0.25 mg kg-1 of scopolamine hydrobromide. A dose of scopolamine hydrobromide (0.06 mg kg-1) or methylbromide (0.25 mg kg-1), pirenzepine dihydrochloride (0.25 mg kg-1) and mecamylamine hydrochloride (0.5 mg kg-1), which per se did not affect gastrointestinal propulsion, antagonized both the stimulating and inhibitory effect of eptastigmine. Thus, the biphasic effect is peripherally mediated through both muscarinic (at least M1) and nicotinic receptors. (C) 2000 Academic Press.
AB - We investigated the influence of increasing oral doses of second generation acetylcholinesterase inhibitors (AChEI) such as tacrine (0.25, 0.5, 1, 2, 3, 4, 10, and 20 mg kg-1), eptastigmine (0.5, 4, 8, 12, 20 and 40 mg kg-1) and E2020 (0.18, 0.25, 0.5, 1, 2, 3, 4 and 10 mg kg-1) on the distance travelled by a charcoal meal administered 30 min after each compound, in comparison with physostigmine (0.5, 1, 2, 4, 8 and 12 mg kg-1). An inverted U regression was observed with a significant parabola between the centimetres travelled and the log of the doses for all AChEI. The maximal stimulating doses (mg kg-1) were 2 for physostigmine, 4 for eptastigmine, 3 for tacrine and E2020, while the inhibitory doses were 12 for physostigmine, 40 for eptastigmine, 20 for tacrine and 10 for E2020. The stimulating and inhibiting effects on gastrointestinal propulsion were significantly reversed by 0.25 mg kg-1 of scopolamine hydrobromide. A dose of scopolamine hydrobromide (0.06 mg kg-1) or methylbromide (0.25 mg kg-1), pirenzepine dihydrochloride (0.25 mg kg-1) and mecamylamine hydrochloride (0.5 mg kg-1), which per se did not affect gastrointestinal propulsion, antagonized both the stimulating and inhibitory effect of eptastigmine. Thus, the biphasic effect is peripherally mediated through both muscarinic (at least M1) and nicotinic receptors. (C) 2000 Academic Press.
KW - Cholinesterase inhibitors
KW - Intestinal transit
KW - Inverted U shape
KW - Peripheral cholinergic mechanism
UR - http://www.scopus.com/inward/record.url?scp=0033848993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033848993&partnerID=8YFLogxK
U2 - 10.1006/phrs.1999.0638
DO - 10.1006/phrs.1999.0638
M3 - Article
C2 - 10816338
AN - SCOPUS:0033848993
VL - 41
SP - 671
EP - 677
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
IS - 6
ER -