Evaluation of the alpha 2-adrenoceptor blocking properties of buspirone and ipsapirone in healthy subjects. Relationship with the plasma concentration of the common metabolite 1-(2-pyrimidinyl)-piperazine
| Autor: | G Schollnhammer, F Cesselin, O Varoquaux, C. Payan, Stephan Chalon, Alain J. Puech, Ivan Berlin |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Agonist medicine.medical_specialty medicine.drug_class Blood Pressure Pharmacology Anxiolytic Clonidine Body Temperature Methoxyhydroxyphenylglycol Buspirone Norepinephrine Double-Blind Method Heart Rate Oral administration Internal medicine medicine Humans Insulin Pharmacology (medical) Adrenergic alpha-Antagonists Analysis of Variance Cross-Over Studies C-Peptide Dose-Response Relationship Drug Chemistry Ipsapirone Antagonist Pyrimidines Endocrinology Anti-Anxiety Agents Growth Hormone 5-HT1A receptor Serotonin Antagonists Research Article medicine.drug |
| Zdroj: | British Journal of Clinical Pharmacology. 39:243-249 |
| ISSN: | 0306-5251 |
| DOI: | 10.1111/j.1365-2125.1995.tb04443.x |
| Popis: | 1. Because the 5-HT1A agonist anxiolytic azapirones have a common alpha 2-adrenoceptor antagonist metabolite, 1-(2-pyrimidinyl)-piperazine (1PP), we measured central and peripheral alpha 2-adrenoceptor dependent responses before and after intravenous administration of 0.15 mg clonidine when healthy subjects were taking buspirone (30 mg day-1 for 4 days and 10 mg on day 5), ipsapirone (15 mg day-1 for 4 days and 5 mg on day 5) or placebo. 2. Clonidine decreased blood pressure, heart rate, oral body temperature, salivary excretion, plasma noradrenaline, 3,4-dihydroxyphenylglycol (DHPG) concentrations, increased plasma growth hormone but did not modify plasma insulin and C-peptide concentrations. Treatments tended to modify only the effect of clonidine on growth hormone (P = 0.07). 3. The azapirones reduced clonidine induced prolongation of choice reaction time (P = 0.015) and tended to antagonise clonidine induced fall in critical flicker fusion frequency (P = 0.066). 4. Only buspirone reduced total reaction time and increased critical flicker fusion threshold measured 12 h after the evening dose and these effects were correlated with the residual plasma 1PP concentration which was higher on buspirone than on ipsapirone (2.76 micrograms l-1, 95% CI:1.3-4.22 vs 0.65 microgram l-1, 95% CI: 0.32-0.98, P = 0.006). 5. Mean AUC of the 1PP plasma concentrations after the last dose of treatments were 3.7 times greater with buspirone than with ipsapirone (P = 0.0011). The AUC ipsapirone/AUC 1PP ratio was 6.45 and the AUC buspirone/AUC 1PP ratio was 0.076.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text