Buspirone-induced hypothermia in normal male volunteers

Young, Allan H.; McShane, Rupert; Park, S.B.; Cowen, Philip J.

doi:10.1016/0006-3223(93)90161-6

Cited by 17 publications

(12 citation statements)

References 7 publications

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“…Flesinoxan-induced hypothermia tends to confirm results from several animal and human studies assessing the effect of different 5-HT 1A receptor agonists on core body temperature (Anderson et al 1990;Lesch et al 1990;Millan et al 1993;Young et al 1993;Kahn et al 1994;Cleare et al 1998;Cryan et al 1999, McAllisterWilliams et al 2001). More specificaly, our results are in agreement with those of Seletti et al (1995), who reported a dose-related decrease in body temperature after administration of flesinoxan (7 and 14 g/kg).…”

Section: Discussionsupporting

confidence: 58%

Hormonal and temperature responses to the 5-HT 1A receptor agonist flesinoxan in normal volunteers

Pitchot¹,

Wauthy²,

Hansenne³

et al. 2002

Psychopharmacology

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Rationale: Flesinoxan is a highly potent and selective 5-HT 1A agonist and appears to be a potentially interesting neuroendocrine serotonergic probe. Objectives: We assessed hormonal (ACTH, cortisol, prolactin and growth hormone) and temperature responses to flesinoxan in normal volunteers. Methods: In a doubleblind placebo-controlled study, single doses of 0.5 mg and 1 mg were injected over 10 min into 12 healthy male volunteers at 1-week intervals. Temperature and hormonal responses were measured at times -30, 0, 15, 30, 60, 90, and 120 min. Results: Flesinoxan induced a significant and dose-dependent increase in adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and a decrease in body temperature. Tolerance to flesinoxan was excellent. Conclusions: These results showed the role of 5-HT 1A mechanisms in the PRL, ACTH, cortisol, GH, and temperature responses to flesinoxan. In the present study, flesinoxan appears a very promising serotonergic neuroendocrine probe.

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Section: Discussionsupporting

confidence: 58%

Hormonal and temperature responses to the 5-HT 1A receptor agonist flesinoxan in normal volunteers

Pitchot¹,

Wauthy²,

Hansenne³

et al. 2002

Psychopharmacology

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“…Both the Rmax and the Rate were predicted to be essentially zero as no response was expected when zero drug is administered. In the studies reported by Young et al (19) and McAllister-Williams and Massay, (20), however, a decrease in core body temperature was observed for the placebo response which explains this poor prediction. Conversely, no such placebo response was observed in the studies conducted by Seletti et al (12) and Pitchot et al (13).…”

Section: Resultsmentioning

confidence: 89%

Allometric Scaling of Pharmacodynamic Responses: Application to 5-Ht1A Receptor Mediated Responses from Rat to Man

et al. 2007

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Purpose. The aim of the present study was to assess whether two widely used biomarkers for 5-HT 1A -receptor mediated responses in the rat (hypothermia and corticosterone increase) could be scaled to man using allometric principles. Materials and Methods. Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) models were developed and characterized in rats for the standard 5-HT 1A -receptor agonists, buspirone and flesinoxan. Allometric scaling was investigated on the basis of simulation taking into account the inter-individual variability and clinical study design. The model-predicted effects of both flesinoxan and buspirone were compared to those published in the literature. Results. The main finding of this analysis was that for both hypothermia and cortisol increase, the model could predict the extent of the pharmacological response in man adequately. For the hypothermic response, the time course of the response was also predicted with a high degree of accuracy. In contrast, in the case of the cortisol response, the observed time lag was, despite the fact that it fell within the model uncertainty, not predicted. Conclusions. Based on these analyses, it is concluded that allometrically scaled mechanism based PK-PD models are promising as a means of predicting the pharmacodynamic responses in man. This approach provides for a novel way of interpreting and scaling pre-clinical pharmacological responses and ultimately facilitates the understanding and prediction of pharmacological responses in man.

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“…It was disappointing that we were unable to demonstrate a hypothermic response. While there is consensus that other 5-HT 1A agonists, including gepirone ), ipsapirone (Lesch et al 1990b;Kahn et al 1994) and flesinoxan (Ansseau et al 1993;Seletti et al 1995) do lower temperature, the effect of buspirone has been inconsistent, with both positive (Young et al 1993) and negative (Lees and Meltzer 1991) results. Why this should be the case is not clear.…”

Section: Discussionmentioning

confidence: 96%

The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers

1996

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We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D2 receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT1A receptor function is reduced by chronic fluvoxamine treatment.

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Buspirone-induced hypothermia in normal male volunteers

Cited by 17 publications

References 7 publications

Hormonal and temperature responses to the 5-HT 1A receptor agonist flesinoxan in normal volunteers

Hormonal and temperature responses to the 5-HT 1A receptor agonist flesinoxan in normal volunteers

Allometric Scaling of Pharmacodynamic Responses: Application to 5-Ht1A Receptor Mediated Responses from Rat to Man

The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers

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