Clinical effects of the 5HT-1A partial agonists, buspirone and gepirone, in the treatment of depression

Robinson, Donald S.; Roberts, Douglas L.; Shrotriya, Rajesh C.; Copp, J.; Wickramaratne, Priya; Alms, Donald R.

doi:10.1016/0006-3223(89)91771-x

Cited by 25 publications

(31 citation statements)

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“…In animal models, agonists of the 5-HT 1A receptor have been shown to produce an antidepressant response through mediation of postsynaptic binding sites, possibly through alteration of second messenger transduction (Kostowski et al 1992;Luscombe et al 1993;Newman et al 1992). The results of limited clinical trials also support a significant role of the 5-HT 1A receptor in depression (Robinson et al 1990). …”

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confidence: 84%

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

Meltzer

Smith

DeKosky

et al. 1998

Neuropsychopharmacology

458

242

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(5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life may contribute to behavioral changes commonly observed in the elderly population. Extensive evidence implicates a deficit in serotonergic neurotransmission in the development of major depression. It has been further suggested that the agerelated changes in 5-HT neurons may predispose the elderly to develop depression. There is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer's disease (AD), with serotonergic dysfunction potentially responsible for a significant portion of the behavioral aspects of the disease. This implication of the 5-HT system in aging and age-related cognitive and mood disorders rests in large part on post mortem studies and animal models, which are limited in their capacity to predict dynamic human biochemical-behavior relationships or to accurately model the living human brain. Initial applications of functional brian imaging with positron emission tomography (PET) in the in vivo study of the brain in aging, depression, and dementia focused on characterizing alterations in physiological measurements of cerebral metabolism and perfusion. However, recent advances in PET radiochemistry, instrumentation, and image processing have paved the way for noninvasive means to test specific hypotheses regarding the direct involvement of 5-HT neurons in the behavioralMajor depression in late life and Alzheimer's disease (AD) are disorders of enormous and increasing public health significance. The prevalence of major depression is estimated at 1% to 10% of persons 60 years of age or older, whereas depressive symptoms may occur in up to 20% (Blazer et al. 1987; Borson et al. 1986; Casey 1994). Substantially higher rates of both major and minor depressions occur among institutionalized aged persons (Parmelee et al. 1989). Furthermore, the rate of suicide in this age group is higher than at any other Address correspondence to: Carolyn Cidis Meltzer, M.D., University of Pittsburgh Medical Center, PET Facility, B-938, 200 Lothrop Street, Pittsburgh, PA 15213-2582. Received March 6, 1997 accepted October 3, 1997. 408 C.C. Meltzer et al.N EUROPSYCHOPHARMACOLOGY 1998 -VOL . 18 , NO . 6 stage of life (Casey 1994). Psychosocial issues such as bereavement, disability, and declining health may serve as contributing factors in the development of geriatric depression (Casey 1994;Gilewski et al. 1991;Kennedy et al. 1991). Ad is truly a disorder of aging, with an incidence of 5% in persons older than 65 years and doubling of disease prevalence every 5 years after age 65; affected individuals represent 20% to 50% of the population after age 80 (Cross and Gurland 1986) (Evans et al. 1989). Costs associated with dementia burden exceed $90 billion annually in the United States (Ernst and Hay 1994). Depression is commonly seen in AD patients and may further interfere with cognitive function, as well as substantially...

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confidence: 84%

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

Meltzer

Smith

DeKosky

et al. 1998

Neuropsychopharmacology

458

242

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“…ln humans, the 5-HTIA agonists of the azapirone class, Le. buspirone, geplrone, and Ipsapirone, have been shown to exert an antldepressant effects ln placebo-controlled triaIs (Amsterdam, 1992;Kurtz et al 1990;Robinson et al 1990). …”

Section: Elfects Of Antidepressant Treatments On 5-ht1a Receptorsmentioning

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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“…Buspirone is currently used clinically for the treatments of anxiety (Goldberg and Finnerty, 1979;Rickels et al, 1982) and depression (Rickels et al, 1991;Robinson et al, 1990). Both anxiolytic and antidepressant effects have been demonstrated in animal models by azapirone compounds, such as buspirone, gepirone, tandospirone, and ipsapirone (reviewed in Lucki, 1991;Traber and Glaser, 1987).…”

Section: Introductionmentioning

confidence: 96%

Chronic administration of the 5-HT1A receptor agonist 8-OH-DPAT differentially desensitizes 5-HT1A autoreceptors of the dorsal and median raphe nuclei

Kreiss

Lucki

1997

Synapse

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The present study investigated alterations of the regulation of serotonin (5-hydroxytryptamine; 5-HT) release by 5-HT1A autoreceptors following single and repeated treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT). Rats were pretreated with 8-OH-DPAT (1.0 mg/kg, s.c.) for 1, 7, or 14 days. The ability of an acute challenge administration of 8-OH-DPAT (1.0 mg/kg, i.p.) to decrease 5-HT release in the ventral striatum and the ventral hippocampus of rats maintained under chloral hydrate anesthesia was examined 24 h after the last pretreatment injection using in vivo microdialysis. The decrease of 5-HT release in the striatum produced by the challenge dose of the 5-HT1A receptor agonist was diminished following 7 and 14 days of pretreatment, but not after 1 day of pretreatment, with 8-OH-DPAT. In contrast, decreases of 5-HT release in the hippocampus by the 8-OH-DPAT challenge were not altered after 1 or 7 days of pretreatment, and only a trend for attenuation appeared after pretreatment for 14 days. The results of the present study indicate that desensitization of 5-HT1A autoreceptors regulating 5-HT release in different brain regions by repeated treatment with 8-OH-DPAT occurs at different rates.

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Clinical effects of the 5HT-1A partial agonists, buspirone and gepirone, in the treatment of depression

Cited by 25 publications

References 0 publications

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

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

Chronic administration of the 5-HT1A receptor agonist 8-OH-DPAT differentially desensitizes 5-HT1A autoreceptors of the dorsal and median raphe nuclei

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