AJP - Regu Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Regul Integr Comp Physiol 281: R2059-R2071, 2001;
0363-6119/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (21)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zuideveld, K. P.
Right arrow Articles by Danhof, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zuideveld, K. P.
Right arrow Articles by Danhof, M.
Vol. 281, Issue 6, R2059-R2071, December 2001

A set-point model with oscillatory behavior predicts the time course of 8-OH-DPAT-induced hypothermia

Klaas P. Zuideveld1, Hugo J. Maas1, Nicoline Treijtel1, Joost Hulshof2, Piet H. van der Graaf1, Lambertus A. Peletier3, and Meindert Danhof1

1 Sylvius Laboratory, Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, 2300 RA Leiden; 2 Department of Mathematics, Free University of Amsterdam, 1081 HV Amsterdam; and 3 Mathematical Institute, Leiden University, 2300 RA Leiden, The Netherlands

Agonists for the 5-hydroxytryptamine (HT)1A receptor induce a hypothermic response that is believed to occur by lowering of the body's set-point temperature. We have developed a physiological model that can be used to predict the complex time course of the hypothermic response after administration of 5-HT1A agonists to rats. In the model, 5-HT1A agonists exert their effect by changing heat loss through a control mechanism with a thermostat signal that is proportional to the difference between measured and set-point temperature. Agonists exert their effect in a direct concentration-dependent manner, with saturation occurring at higher concentrations. On the basis of simulations, it is shown that, depending on the concentration and the intrinsic efficacy of a 5-HT1A agonist, the model shows oscillatory behavior. The model was successfully applied to characterize the complex hypothermic response profiles after administration of the reference 5-HT1A agonists R-8-hydroxy-2-(di-n-propylamino)tetralin (R-8-OH-DPAT) and S-8-OH-DPAT. This analysis revealed that the observed difference in effect vs. time profile for these two reference agonists could be explained by a difference in in vivo intrinsic efficacy.

pharmacokinetic-pharmacodynamic modeling; 5-hydroxytryptamine1A receptor; R-8-hydroxy-2-(di-n-propylamino)tetralin; S-8-hydroxy-2-(di-n-propylamino)tetralin


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
K. P. Zuideveld, P. H. Van der Graaf, D. Newgreen, R. Thurlow, N. Petty, P. Jordan, L. A. Peletier, and M. Danhof
Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of 5-HT1A Receptor Agonists: Estimation of in Vivo Affinity and Intrinsic Efficacy on Body Temperature in Rats
J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 1012 - 1020.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
D. E. Mager, E. Wyska, and W. J. Jusko
Diversity of Mechanism-Based Pharmacodynamic Models
Drug Metab. Dispos., May 1, 2003; 31(5): 510 - 518.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. C. Nicholas and L. S. Seiden
Ambient Temperature Influences Core Body Temperature Response in Rat Lines Bred for Differences in Sensitivity to 8-Hydroxy-dipropylaminotetralin
J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 368 - 374.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
S.A.G. Visser, F.L.C. Wolters, J. M. Gubbens-Stibbe, E. Tukker, P. H. van der Graaf, L. A. Peletier, and M. Danhof
Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABAA Receptor Modulators: In Vitro-in Vivo Correlations
J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 88 - 101.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. P. Zuideveld, J. Rusic-Pavletic, H. J. Maas, L. A. Peletier, P. H. Van der Graaf, and M. Danhof
Pharmacokinetic-Pharmacodynamic Modeling of Buspirone and Its Metabolite 1-(2-Pyrimidinyl)-piperazine in Rats
J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 1130 - 1137.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. A. G. Visser, W. W. F. T. Gladdines, P. H. van der Graaf, L. A. Peletier, and M. Danhof
Neuroactive Steroids Differ in Potency but Not in Intrinsic Efficacy at the GABAA Receptor in Vivo
J. Pharmacol. Exp. Ther., November 1, 2002; 303(2): 616 - 626.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. A. G. Visser, C. J. G. M. Smulders, B. P. R. Reijers, P. H. van der Graaf, L. A. Peletier, and M. Danhof
Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of Concentration-Dependent Hysteresis and Biphasic Electroencephalogram Effects of Alphaxalone in Rats
J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 1158 - 1167.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. P. Zuideveld, N. Treijtel, H. J. Maas, J. M. Gubbens-Stibbe, L. A. Peletier, P. H. van der Graaf, and M. Danhof
A Competitive Interaction Model Predicts the Effect of WAY-100,635 on the Time Course of R-(+)-8-Hydroxy-2-(di-n-propylamino)tetralin-Induced Hypothermia
J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 330 - 338.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online