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Is it possible to predict the clinical effects of neuroleptics from animal data? Part V: From haloperidol and pipamperone to risperidone.
- Source :
-
Arzneimittel-Forschung [Arzneimittelforschung] 1994 Mar; Vol. 44 (3), pp. 269-77. - Publication Year :
- 1994
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Abstract
- In 1965 the first study of this series reported different effects of neuroleptics in rats, supporting clinical differences. At the one end, haloperidol presented as a potent and specific antagonist of the psychostimulants amphetamine and apomorphine. Haloperidol-like neuroleptics have marked effects on psychomotor agitation, delusions and hallucinations and bind with high affinity to dopamine-D2 receptors. Pipamperone, at the other end, presented with weak "dopamine" antagonism and more striking tryptamine antagonism. Pipamperone is known to improve disturbed sleep, social withdrawal and other symptoms of chronic schizophrenia in the relative absence of extrapyramidal symptoms. These effects have been attributed to central serotonin-S2 antagonism, on the basis of the clinical effects of ritanserin. As shown by the present analysis of relative tryptamine versus apomorphine antagonism of 57 neuroleptics, in comparison to relative S2 vs. D2 binding, there is a continuity in the series. About 30% of the compounds can be considered to act primarily as serotonin antagonists, but few are markedly more potent than pipamperone. In amphetamine-challenged rats pipamperone-like activity is reflected in preferential inhibition of the excessive oxygen consumption rather than of agitation. Risperidone inhibits oxygen consumption (0.016 mg/kg) at the same dose as haloperidol inhibits agitation. Other low-dose effects of risperidone include reversal of amphetamine-induced withdrawal, antagonism of agitation induced by a sequential tryptamine and apomorphine challenge and LSD-antagonism. In dogs, the antiemetic activity of risperidone is characterized by high oral effectiveness which lasts one day and agrees with pharmacokinetic data when allowance is made for the active metabolite 9-hydroxyrisperidone.(ABSTRACT TRUNCATED AT 250 WORDS)
- Subjects :
- Amphetamine antagonists & inhibitors
Animals
Antipsychotic Agents pharmacokinetics
Antipsychotic Agents therapeutic use
Apomorphine antagonists & inhibitors
Apomorphine pharmacology
Butyrophenones pharmacokinetics
Butyrophenones therapeutic use
Dogs
Dopamine D2 Receptor Antagonists
Haloperidol pharmacokinetics
Haloperidol therapeutic use
Humans
In Vitro Techniques
Isoxazoles pharmacokinetics
Isoxazoles therapeutic use
Lysergic Acid Diethylamide antagonists & inhibitors
Motor Activity drug effects
Neostriatum drug effects
Neostriatum metabolism
Oxygen Consumption drug effects
Piperidines pharmacokinetics
Piperidines therapeutic use
Rats
Risperidone
Schizophrenia drug therapy
Serotonin Antagonists
Species Specificity
Tryptamines antagonists & inhibitors
Tryptamines pharmacology
Antipsychotic Agents pharmacology
Butyrophenones pharmacology
Haloperidol pharmacology
Isoxazoles pharmacology
Piperidines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0004-4172
- Volume :
- 44
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Arzneimittel-Forschung
- Publication Type :
- Academic Journal
- Accession number :
- 7514873