Abstract |
Pancopride ((+-)N-(1-azabicyclo-[2,2,2]-oct-3-yl)-2-cyclopropylmethoxy-4-ami no-5-chlorobenzamide) is a new potent and selective 5-HT3 receptor antagonist, orally and parenterally effective against cytotoxic drug-induced emesis. In vitro, pancopride displayed high affinity (Ki = 0.40 nM) for [3H] GR65630-labelled 5-HT3 recognition sites in membranes from the cortex of rat brains. In vivo, pancopride antagonized 5-HT-induced bradycardia in anaesthetized rats when administered i.v. 5 min (ID50 = 0.56 microgram/kg) or p.o. 60 min (ID50 = 8.7 micrograms/kg) before 5-HT challenge. A single oral dose (10 micrograms/kg) of pancopride produced a significant inhibition of the bradycardic reflex over an 8-h period. Pancopride dose dependently inhibited the number of vomiting episodes and delayed the onset of vomiting induced by cisplatin in dogs (ID50 = 3.6 micrograms/kg i.v. and 7.1 micrograms/kg p.o.). Pancopride was also effective in blocking mechlorethamine- and dacarbazine-induced emesis. Unlike metoclopramide, pancopride was shown to lack any measurable antidopaminergic activity both in vitro and in vivo. These results support clinical data, indicating that pancopride will be a useful drug for treating cytostatic-induced emesis in humans.
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Authors | A G Fernández, J Puig, J Beleta, T Doménech, J Bou, P Berga, R W Gristwood, D J Roberts |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 222
Issue 2-3
Pg. 257-64
(Nov 10 1992)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 1451737
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antiemetics
- Benzamides
- Bridged Bicyclo Compounds
- Bridged Bicyclo Compounds, Heterocyclic
- Receptors, Serotonin
- Serotonin Antagonists
- pancopride
- Metoclopramide
- Cisplatin
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Topics |
- Animals
- Antiemetics
(metabolism, pharmacology)
- Benzamides
(metabolism, pharmacology)
- Bridged Bicyclo Compounds
(metabolism, pharmacology)
- Bridged Bicyclo Compounds, Heterocyclic
- Cisplatin
(adverse effects)
- Dogs
- Guinea Pigs
- Male
- Metoclopramide
(metabolism, pharmacology)
- Rabbits
- Rats
- Rats, Wistar
- Receptors, Serotonin
(drug effects, metabolism)
- Serotonin Antagonists
(metabolism, pharmacology)
- Swine
- Vomiting
(chemically induced, prevention & control)
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