Comparative effects of serotonergic agonists withvarying efficacy at the                     5-HT<sub>1A</sub> receptor on core body temperature: modification by the                 selective 5-HT<sub>1A</sub> receptor antagonist WAY 100635

Cryan, John F.; Kelliher, Padraig; Kelly, John; Leonard, Brian E.

doi:10.1177/026988119901300310

Cited by 68 publications

(38 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 59%

“…This hypothermic effect is probably mediated through the stimulation of 5-HT 1A receptors. Indeed, recently, Cryan et al (1999) demonstrated that pretreatment with the selective 5-HT 1A receptor antagonist WAY 100635 blocked hypothermic response to flesinoxan in rats. Moreover, flesinoxaninduced hypothermia could be due at least in part to the stimulation of somatodendritic 5-HT 1A receptors (Cowen 2000).…”

Section: Discussionmentioning

confidence: 99%

“…In the rat, both pre-and postsynaptic receptors have been implicated (Bill et al 1991;Millan et al 1993;McAllister-Williams et al 2001), and in the mouse hypothermic response is mediated via cell body 5-HT 1A receptors (Goodwin et al 1987;Martin et al 1992). However, overall, temperature response to flesinoxan could be used as a relatively direct, simple and robust measure of 5-HT 1A receptor sensitivity (Cryan et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence from several functional models indicate that flesinoxan behaves as a full agonist at the 5-HT 1A receptor, both pre-and postsynaptically (Hadrava et al 1995). In rats, flesinoxan increases prolactin levels at low doses and is able to induce a hypothermic response comparable to that of 8-hydroxy-2-(di-n-propylamino)tertralin (8-OH-DPAT) (Cryan et al 1999). In humans, after oral intake, the distribution half-life of flesinoxan is about 2 h and its elimination half-life is about 9 h. Moreover, in contrast to most azapirones, flesinoxan is not metabolized into 1-phenylpiperazine (1-PP), and is available for intravenous use.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Pitchot¹,

Wauthy²,

Hansenne³

et al. 2002

Psychopharmacology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Pitchot¹,

Wauthy²,

Hansenne³

et al. 2002

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…2 Ipsapirone induces cortisol secretion via release of ACTH rather than by direct action on the adrenal gland (Przegalinski et al 1989). The assumption that ipsapirone's hypothermic effect and the stimulation of ACTH and cortisol primarily reflect 5-HT 1A receptor function is also supported by the observation that these responses can be antagonized by 5-HT 1A receptor antagonists (Goodwin et al 1987;Hamon et al 1987) and by recent findings confirming the utility of hypothermia as a robust in-vivo probe of 5-HT-1A receptor function (Cryan et al 1999;Oerther and Ahlenius 2001). However, further studies are necessary to clarify whether cortisol and temperature responses are mediated by different mechanisms (Cowen 2001).…”

mentioning

confidence: 89%

Smoking Modulates Neuroendocrine Responses to Ipsapirone in Patients with Panic Disorder

Broocks

Bandelow

Koch

et al. 2002

Neuropsychopharmacology

View full text Add to dashboard Cite

Reduced 5-HT1A-receptor responsiveness has been reported in patients with panic disorder(PD) and/or agoraphobia (PDA). Although many of these patients are regular smokers, it has not been examined whether psychological or neurobiological effects induced by the selective 5-HT1A-receptor agonist, ipsapirone, are affected by the smoking status of the patients.In order to clarify this question neuroendocrine challenges with oral doses of ipsapirone (0.3 mg/kg) Neuropharmacological challenges with the selective 5-hydroxytryptamine-1A (5-HT1A) receptor agonist, ipsapirone, have been used in several studies to assess 5-HT1A-receptor related functions in patients suffering from various neuropsychiatric disorders (Broocks et al. 2000;Lesch et al. 1990a;Lesch et al. 1991;Lesch et al. 1990b;Lesch et al. 1992) and in healthy controls (Broocks et al. 1999;Kahn et al. 1994;Lesch et al. 1990c;Lesch et al. 1990d).Indices of abnormal serotonergic function have been reported in patients with panic disorder (PD) and/or agoraphobia (PDA). In particular, there is evidence for an increased sensitivity of the 5-HT 2C subsystem (Charney et al. 1987a;Charney et al. 1987b;Kahn et al. 1988a Kahn and Wetzler 1991;Kahn et al. 1988b). In contrast, stimulation of 5-HT 1A receptors by ipsapirone was followed by an attenuated hypothermic and ACTH/cortisol response in patients with PDA (Broocks et al. 2000;Lesch et al. 1992). In healthy controls, ipsapirone produces dose-dependent increases in plasma cortisol and ACTH as well as dose-dependent reductions in body temperature (Cowen 2001;Kahn et al. 1994;Lesch et al. 1989). Ipsapirone acts on specific serotonergic mechanisms in the brain through its high-affinity binding to the 5-HT 1A receptor subtype. The binding sites are predominantly located on serotonergic neurons in the raphe nuclei (presynaptic autoreceptors) and in limbic structures (postsynaptic receptors). Agonistic properties at presynaptic somatodendritic sites have been observed, resulting in decreased serotonergic neurotransmission (Peroutka 1985). Concerning the high selectivity of ipsapirone, it has to be considered that the metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) has been found to exert antagonistic effects at pre-and postsynaptic ␣ 2-adrenoceptors (Blier et al. 1991;Miller et al. 1992).Several lines of evidence suggest that serotonergic neurotransmission, including the regulation of 5-HT1A receptors, is affected by nicotine (Benwell et al. 1990;Kenny et al. 2001). Recent studies show that some of nicotine's psychotropic and endocrine effects are exerted by stimulation of 5-HT1A receptors on dorsal raphe neurons (Cheeta et al. 2001;Mihailescu et al. 2001).There is a high incidence of smoking in patients with anxiety and other psychiatric disorders (Breslau et al. 1993;Glassman 1993;Kendler et al. 1993;Marks et al. 1997;Miller and Gold 1998;Sellman et al. 1999). To our knowledge, no clinical studies have examined the question of whether psychological or neurobiological effects induced by serotonergic agents such as ipsapi...

show abstract

Induction of hypothermic conditions associated with increased micronuclei formation in sigma‐1 receptor knockout mice after administration of the antipsychotic compound E‐5842

Guzmán¹,

Marín²,

Garcı́a³

et al. 2008

Environ and Mol Mutagen

View full text Add to dashboard Cite

The antipsychotic sigma-1 (sigma(1)) receptor ligand E-5842 has been shown to increase micronucleated polychromatic erythrocyte (MNPCE) frequency in mouse bone marrow secondary to compound-induced hypothermia. Interaction with sigma(1) receptor has been considered a plausible contributing factor for E-5842-induced hypothermia, raising concern for a possible class effect of sigma receptor ligands in the mouse micronucleus (MN) test. We assessed the potential of E-5842 (200 mg/kg, oral) to produce hypothermic conditions associated with increased micronuclei formation in sigma(1) receptor knockout (sigma(1)R-KO) and wild type (WT) mice. After administration, animal's rectal temperature was recorded and peripheral blood and bone marrow samples were obtained (48 hr) and assessed for induction of micronucleated reticulocytes (MNRET) and MNPCE, respectively. E-5842 administration produced marked hypothermia both in sigma(1)R-KO and WT mice. Maximum decreases from preadministration temperature were 12.2 and 13.5 degrees C in sigma(1)R-KO and WT mice, respectively. Temperature returned to normal approximately 32 hr after administration. Bone marrow examination revealed a statistical significant increase (P < 0.05) in MNPCE frequency both in sigma(1)R-KO and WT animals. Examination of peripheral blood samples showed a slight, although nonstatistical significant, increase in MNRET frequency in sigma(1)R-KO mice. No similar effect was observed among WT animals. The results obtained after E-5842 administration to sigma(1)R-KO mice indicate that induction of hypothermic conditions associated with increased MNPCE formation is not mediated by compound interaction with sigma(1) receptor, ruling out concern for a possible class effect of similar high affinity sigma(1) receptor ligands in the mouse MN test.

show abstract

Comparative effects of serotonergic agonists withvarying efficacy at the 5-HT_1A receptor on core body temperature: modification by the selective 5-HT_1A receptor antagonist WAY 100635

Cited by 68 publications

References 31 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

Smoking Modulates Neuroendocrine Responses to Ipsapirone in Patients with Panic Disorder

Induction of hypothermic conditions associated with increased micronuclei formation in sigma‐1 receptor knockout mice after administration of the antipsychotic compound E‐5842

Contact Info

Product

Resources

About

Comparative effects of serotonergic agonists withvarying efficacy at the 5-HT1A receptor on core body temperature: modification by the selective 5-HT1A receptor antagonist WAY 100635

Cited by 68 publications

References 31 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

Smoking Modulates Neuroendocrine Responses to Ipsapirone in Patients with Panic Disorder

Induction of hypothermic conditions associated with increased micronuclei formation in sigma‐1 receptor knockout mice after administration of the antipsychotic compound E‐5842

Contact Info

Product

Resources

About

Comparative effects of serotonergic agonists withvarying efficacy at the 5-HT_1A receptor on core body temperature: modification by the selective 5-HT_1A receptor antagonist WAY 100635