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Clonidine-induced emesis: a multitransmitter pathway concept
N Japundzić-Zigon1, R Samardzić, D B Beleslin
1Department of Pharmacology, Faculty of Medicine, Belgrade, Yugoslavia.
Pharmacological Research
|April 1, 1997
Summary
Clonidine triggers vomiting in cats via multiple neurotransmitter pathways, including cholinergic and noradrenergic systems, acting on receptors outside the area postrema. These findings reveal complex central mechanisms regulating emesis.
Area of Science:
- Neuroscience
- Pharmacology
- Neurotransmission
Background:
- Clonidine, an alpha-2 adrenoceptor agonist, is known to induce emesis.
- The precise central pathways and receptor interactions involved in clonidine-induced emesis remain incompletely understood.
Purpose of the Study:
- To investigate the neurochemical mechanisms underlying clonidine-induced emesis in unanaesthetized cats.
- To identify specific neurotransmitter systems and receptor subtypes involved in mediating this effect.
Main Methods:
- Clonidine was administered intracerebroventricularly (ICV) in cats.
- Various receptor antagonists (alpha-adrenoceptor blockers, antimuscarinic, dopamine, serotonin, histamine antagonists), ganglionic blocker, and opioid antagonist were administered ICV.
- Area postrema ablation was performed, and neurotransmitter synthesis/storage inhibitors (alpha-methyl-p-tyrosine, hemicholinium-3, reserpine, 5,6-dihydroxytryptamine) were used.
Main Results:
- Clonidine induced dose-dependent emesis, which was not abolished by area postrema ablation.
- Alpha-2 and mixed alpha-1/alpha-2 adrenoceptor antagonists, antimuscarinic, serotonin, and histamine antagonists attenuated clonidine-induced emesis.
- Cholinergic and noradrenergic mechanisms, along with alpha-adrenoceptors, muscarinic, serotonin, and histamine receptors (H1/H2), were implicated in mediating the emetic response.
Conclusions:
- Cholinergic and noradrenergic pathways are crucial for clonidine-induced emesis.
- The emetic effect involves multiple receptor types, including alpha-adrenoceptors, muscarinic cholinoceptors, serotonin receptors, and histamine H1/H2 receptors.
- These receptors likely function presynaptically outside the area postrema to initiate emetic impulses.
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