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PMID: 6918 Published · ppublish English Journal Article

Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 292 ·No. 1 ·1976-00-00 ·Pages 43-52

Andén NE, Grabowska M, Strömbom U

Abstract

The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. 2. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). 3. The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones.

MeSH Terms
Adrenergic alpha-Antagonists/pharmacology Animals Brain/metabolism Central Nervous System/drug effects Clonidine/antagonists & inhibitors,pharmacology Dihydroxyphenylalanine/metabolism Dioxanes/pharmacology Dopamine/metabolism Female Haloperidol/pharmacology Male Methyltyrosines/pharmacology Mice Motor Activity/drug effects Norepinephrine/metabolism Phenoxybenzamine/pharmacology Piperidines/pharmacology Rats Receptors, Adrenergic/drug effects Reflex/drug effects Spinal Cord/metabolism Tolazoline/pharmacology Yohimbine/pharmacology
Chemicals
Adrenergic alpha-Antagonists Dioxanes Methyltyrosines Piperidines Receptors, Adrenergic Phenoxybenzamine Yohimbine Dihydroxyphenylalanine Tolazoline Haloperidol Clonidine Dopamine Norepinephrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Andén N E
Grabowska M
Strömbom U
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45 references, click to expand
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Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00506488
Published
1976-00-00
Pages
43-52
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00506488 View journal details
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