An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression

Grof, Paul; Joffe, Russell T.; Kennedy, Samantha; Persad, Emmanuel; Syrotiuk, J.; Bradford, Daniel

doi:10.1097/00004850-199300830-00005

Cited by 51 publications

(28 citation statements)

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“…The potential antldepressant propertlcs of flesinoxan have been assessed in several animal models of depression (van Hest et al 1992). ln h umans with anxiety disorders or wlth major depression, flesinoxan showed therapeutic effects (Graf et al 1993;Ansseau et al 1993;Bradford, 1992). …”

Section: Flesinoxanmentioning

confidence: 99%

Serotonin1A Receptor Activation by Flesinoxan in Humans Body Temperature and Neuroendocrine Responses

Seletti

Benkelfat

Blier

et al. 1995

Neuropsychopharmacology

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Section: Flesinoxanmentioning

confidence: 99%

Serotonin1A Receptor Activation by Flesinoxan in Humans Body Temperature and Neuroendocrine Responses

Seletti

Benkelfat

Blier

et al. 1995

Neuropsychopharmacology

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“…These conflicting results raise the question as to which rodent model will more closely resemble humans. Flesinoxan is currently being investigated as a potential antidepressant in humans (Baumann and Bertschy 1997;Grof et al 1993). Thus, assessment of the effects of flesinoxan on PPI in humans might soon be possible.…”

mentioning

confidence: 99%

Knockout Mice Reveal Opposite Roles for Serotonin 1A and 1B Receptors in Prepulse Inhibition

Dulawa

Gross

Stark

et al. 2000

Neuropsychopharmacology

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The serotonergic system is involved in the modulation of prepulse inhibition (PPI) Anpirtoline; 8-OH-DPAT; Flesinoxan; RU 24969 Sensorimotor gating is a form of central nervous system inhibition that "gates" or filters out excessive sensory, motor, and cognitive information to sustain mental and behavioral integration. Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is the reduction in startle amplitude that results when an abrupt startling stimulus is preceded 30-500 msec by a nonstartling prepulse (Graham 1975). Patients with several neuropsychiatric disorders, including schizophrenia (Braff et al. 1978Bolino et al. 1994), schizotypal personality disorder (Cadenhead et al. 1993), and obsessive compulsive disorder (Swerdlow 1995) exhibit PPI deficits. Startle habituation, a simple form of learning, which refers to the decrement in startle responding to repeated presentations of an initially novel and intense stimulus (Thorpe 1956), is also deficient in schizophrenia and schizotypal patients Cadenhead et al. 1993;Geyer and Braff 1982;Bolino et al. 1994). Further investigation of the neural substrates modulating PPI may provide insight into the pathophysiology of the sensorimotor gating deficits in these syndromes.Serotonin 1A (5-HT 1A ) and serotonin 1B (5-HT 1B ) receptors have been suggested to contribute to the modulation of PPI. For instance, the 5-HT 1A agonist 8-OH-DPAT decreases PPI in rats (Rigdon and Weatherspoon 1992;Sipes and Geyer 1995), but increases PPI in mice (Dulawa et al. 1997(Dulawa et al. , 1998. However, 8-OH-DPAT also has affinity for 5-HT 7 receptors (Tsou et al. 1994;Ying and Rusak 1997 Received August 27, 1999; revised November 29, 1999; accepted December 6, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 6 Opposite Roles for 5-HT1A and 1B Receptors in Murine PPI 651 5-HT 1B knockout (1BKO) mice (Dulawa et al. 1997), suggesting that 5-HT 1B receptors modulate both forms of startle plasticity in mice.The recent availability of 5-HT 1A knockout (1AKO) mice (Ramboz et al. 1998;Heisler et al. 1998;Parks et al. 1998) and the selective 5-HT 1B agonist anpirtoline (Schlicker et al. 1992) permits more precise dissection of the roles of 5-HT 1A and 5-HT 1B receptors in behaviors of interest. 5-HT 1A receptors are autoreceptors and heteroreceptors for serotonergic and nonserotonergic neurons and are located on cell bodies and dendrites, where they inhibit cell firing (Hamon et al. 1990). 5-HT 1B receptors are autoreceptors and heteroreceptors expressed on axon terminals that inhibit neurotransmitter release (Boschert et al. 1994;Hen 1992). The densest localization of 5-HT 1A receptors is in the hippocampus, dorsal raphe, interpeduncular nucleus, and lateral septum (Ramboz et al. 1998). 5-HT 1B receptors are most densely localized on striatal neuron terminals in the globus pallidus and substantia nigra, and on Purkinje neuron terminals in the deep cerebellar nuclei (Boschert et al. 1994;Pazos et al. 1988). Many of these brain regions, such as the hippoca...

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“…They presented reduced total immobility time on the forced swimming test [73]. This therapeutic action may be associated with the desensitization effect of the 5-HT 1A -R in the nucleus of the dorsal raphe as an action mechanism [71].…”

Section: Serotonin -A Chemical Messenger Between All Types Of Living mentioning

confidence: 85%

“…This drug has total antagonism to 5-HT 1A -R with high affinity [70]. Various studies have demonstrated its antidepressant properties, particularly in treatment-resistant DDM patients [71]. For example, in a double-blind, placebo-controlled and fixed-dose study of treatment-resistant DDM patients, flesinoxan (1.2 mg/day) administered for 6 weeks improved scores on the HAM-D17, MontgomeryAsberg Depression Rating Scale (MADRS) and CGI scales with improvement in subjects' mood.…”

Section: Serotonin -A Chemical Messenger Between All Types Of Living mentioning

confidence: 99%

Association of 5-HT1A Receptors with Affective Disorders

Soria-Fregozo¹,

Vega²,

FranciscoRodríguez-Landa³

et al. 2017

Serotonin - A Chemical Messenger Between All Types of Living Cells

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Serotonin or 5-hydroxytryptamine (5-HT) is synthesized in both the brain and peripheral system, which exert their actions at a wide family of receptors classified as 5-HT 1 to 5-HT 7 . Pharmacological, behavioral, and clinical studies involve particularly to the 5-HT 1A receptors (5-HT 1A -R) -auto-receptors (presynaptic) and heteroreceptors (postsynaptic) -in the control of motivated behavior, and consequently in the physiopathology of affective disorders and in the action mechanism of antidepressant drugs. In this way, some research support that 5-HT 1A -R participates in the delayed effect of different types of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), and tricyclic drugs, principally. The therapeutic effect of serotonergic drugs as the SSRIs, starting with the binding to auto-receptors, which produces increases of 5-HT in the synaptic cleft as consequence of blockade of serotonin reuptake. While these molecular events occur initially, in the long-term are produced plastic changes at neuronal level, as well as down-regulation of the 5-HT 1A -R, which is associated with the therapeutic effects of antidepressant drugs. The purpose of this chapter is to analyze and discuss the current information about of 5-HT 1A -R-mediated signaling cascades, the intracellular signaling of 5-HT 1A -R, in addition to their expression and pharmacology that are important to treatment of affective disorders symptoms.

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An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression

Cited by 51 publications

References 0 publications

Serotonin1A Receptor Activation by Flesinoxan in Humans Body Temperature and Neuroendocrine Responses

Serotonin1A Receptor Activation by Flesinoxan in Humans Body Temperature and Neuroendocrine Responses

Knockout Mice Reveal Opposite Roles for Serotonin 1A and 1B Receptors in Prepulse Inhibition

Association of 5-HT1A Receptors with Affective Disorders

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