A comparison of the neuro‐endocrinological and temperature effects of DU 29894, flesinoxan, sulpiride and haloperidol in normal volunteers.

Koning, P de; Vries, M. Hugo de

doi:10.1111/j.1365-2125.1995.tb04403.x

Cited by 26 publications

(23 citation statements)

References 20 publications

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“…Furthermore, a single 0.5 mg dose produces similar EEG activity to 20 mg buspirone (Solvay Pharmaceuticals, 1997). We did not find the significant increases in GH (actually reduced) and cortisol previously described with 1 mg oral flesinoxan (de Koning and de Vries, 1995). This is presumably because of our smaller sample size.…”

Section: Discussioncontrasting

confidence: 83%

“…This relatively poor penetration appears to arise because flesinoxan is a substrate for P-glycoprotein, a multidrug transporter, which actively effluxes it from the brain at the blood-brain barrier (van der Sandt et al, 2001). In man, the evidence that flesinoxan crosses the bloodbrain barrier is indirect: it causes elevation of ACTH, cortisol, and growth hormone while reducing temperature by mechanisms that are believed to be centrally mediated (de Koning and de Vries, 1995;Pitchot et al, 2002;Seletti et al, 1995). Furthermore, a single 0.5 mg dose produces similar EEG activity to 20 mg buspirone (Solvay Pharmaceuticals, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…In man, 1 mg intravenous flesinoxan produces a 5-HT 1A agonist profile: it significantly elevates adrenocorticotropic hormone, cortisol, growth hormone, and prolactin while reducing temperature (Pitchot et al, 2002;Seletti et al, 1995). A 1 mg oral dose behaves similarly but does not elevate prolactin (de Koning and de Vries, 1995). Results from phase II studies for depression and generalized anxiety disorder have been encouraging: those from phase III studies are not yet available (Pitsikas, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Occupancy of Agonist Drugs at the 5-HT1A Receptor

Bantick

Rabiner

Hirani

et al. 2003

Neuropsychopharmacol

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Drugs acting on the 5-HT 1A receptor are used in the treatment of depression, generalized anxiety disorder, and schizophrenia. This study investigated 5-HT 1A receptor occupancy by the 5-HT 1A agonist drugs flesinoxan (a highly selective probe for the 5-HT 1A receptor) and ziprasidone (a novel atypical antipsychotic drug). Using a within-subject design, 14 healthy volunteers each received two positron emission tomography scans using the selective 5-HT 1A antagonist radiotracer [ 11 C]WAY-100635. One scan constituted a baseline, while the other followed either 1 mg flesinoxan or 40 mg ziprasidone orally. In addition, rats were pretreated with intravenous flesinoxan at doses ranging from 0.001 to 5 mg/kg then [ 11 C]WAY-100635 binding measured ex vivo. Cerebral cortical and hippocampal regions of interest, and cerebellar reference regions were sampled to estimate 5-HT 1A receptor occupancy (inferred from reductions in specific radioligand binding). In man, occupancy was not significant despite volunteers experiencing side effects consistent with central serotonergic activity. The mean cerebral cortex occupancy (71 SD) for flesinoxan was 8.7% (713%), and for ziprasidone 4.6% (717%). However, in rats, flesinoxan achieved significant and dose-related occupancy (17-57%) at 0.25 mg/kg and above. We conclude that 5-HT 1A receptor agonists produce detectable occupancy only at higher doses that would produce unacceptable levels of side effects in man, although lower doses are sufficient to produce pharmacological effects. The development of agonist radiotracers may increase the sensitivity of detecting agonist binding, as 5-HT 1A antagonists bind equally to low-and high-affinity receptor states, while agonists bind preferentially to the high-affinity state.

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Section: Discussioncontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Occupancy of Agonist Drugs at the 5-HT1A Receptor

Bantick

Rabiner

Hirani

et al. 2003

Neuropsychopharmacol

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“…The hypothermic effects of several 5-HT 1A agonists in humans have been well reported, including buspirone (Young et al 1994;Anderson et al 1996), ipsapirone (Meltzer and Maes 1995;Lerer et al 1999;Shapira et al 2000), gepirone (Anderson et al 1990) and flesinoxan (de Koning and de Vries 1995;Pitchot et al 1995;Seletti et al 1995). However the effect of pindolol on body temperature has been much less studied.…”

Section: Discussionmentioning

confidence: 97%

EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans

McAllister-Williams

Massey

2003

Psychopharmacology

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The data obtained are consistent with the EEG effects of buspirone and pindolol being mediated by somatodendritic 5-HT(1A) receptors, in contrast to the neuroendocrine response, which is known to be mediated by postsynaptic receptors. The development of this novel method of assessing somatodendritic 5-HT(1A) receptors in humans is a potentially important advance which may allow the testing of hypotheses of its involvement in depression and response to antidepressants.

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“…This indicates that orexin A controls various functions [11,12] including regulation of sleep/wake cycle [13]. Neuroleptic drugs, as haloperidol, clozapine, olanzapine, risperidone and quetiapine, can modify body temperature, as showed by various experimental models [14][15][16][17][18][19]. In the present mini-review, we summarize our published data in an unique report so to emphasize the influences of these neuroleptic drugs on the control of body temperature, exerted by orexinergic system.…”

Section: Introductionmentioning

confidence: 99%

Neuroleptic Drugs Affect Sympathetic and Thermogenic Reactions to Orexin A

S¹

2014

J Psychiatry

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This review of our literature describes the effects of many neuroleptic drugs on the sympathetic and hyperthermic reactions due to orexin A, a neuropeptide affecting body temperature and food intake by an increase in sympathetic activity. Haloperidol reduces, while clozapine and olanzapine block the hyperthermia induced by orexin A. Risperidone enhances the elevation of body temperature due to orexin A. Quetiapine delays these hyperthermic effects. The implications on human therapeutic strategies are discussed, including the involvement of orexinergic pathway in the induction of obesity, induced by these neuroleptic substances. We summarize our published data in a unique report so to emphasize the influences of these neuroleptic drugs on the control of body temperature, exerted by orexinergic system. This large vision could be also useful to address therapeutic choices.Patients with serious mental illness are at higher risk of developing metabolic abnormalities (e.g., weight gain, increased blood pressure, and glucose or lipid levels) in comparison to general population. Since the risk increases following initiation of narcoleptic therapy, it must assess carefully risks and benefits when choosing a particular antipsychotic drug.

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A comparison of the neuro‐endocrinological and temperature effects of DU 29894, flesinoxan, sulpiride and haloperidol in normal volunteers.

Cited by 26 publications

References 20 publications

Occupancy of Agonist Drugs at the 5-HT1A Receptor

Occupancy of Agonist Drugs at the 5-HT1A Receptor

EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans

Neuroleptic Drugs Affect Sympathetic and Thermogenic Reactions to Orexin A

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