Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents

Fernández, Javier; Alonso, J.M.; Andrés, Juvenal; Cid, José M.; Dı́az, Adolfo; Iturrino, Laura; Gil, Pilar; Megens, Anton; Sipido, V.; Trabanco, Andrés A.

doi:10.1021/jm049632c

Cited by 67 publications

(28 citation statements)

References 15 publications

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“…Mianserin also binds to α 2C , 5-HT 2C , α 2A , 5-HT 3 , 5-HT 7 , D 1 , D 2 , and D 3 receptors (Kd of 3.8, 4.4, 4.8, 7.1, and 56 nM, and 1.4, 2.2, and 2.8 μ M, resp.) [510, 511]. Because of the high affinity of mianserin to all of these receptors, the primary mechanism of action of the compound is not related to its effect on monoamine transporters.…”

Section: Net Inhibitorsmentioning

confidence: 99%

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Monoamine Reuptake Inhibitors in Parkinson’s Disease

Huot

Fox

Brotchie

2015

Parkinson's Disease

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The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia.

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Section: Net Inhibitorsmentioning

confidence: 99%

“…Mirtazapine also binds to 5-HT 3 , 5-HT 2C , 5-HT 2A , 5-HT 7 , D 1 , and D 3 receptors (Kd of 7.94, 39, 69, and 265 nM and 4.2 and 5.7 μ M, resp.) [510, 511]. In addition, mirtazapine displays affinity for 5-HT 2B , 5-HT 1A , 5-HT 1B , and H 2 receptors (Kd of 199 nM, and 5.0, 12, and 16 μ M, resp.)…”

Section: Net Inhibitorsmentioning

confidence: 99%

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Huot

Fox

Brotchie

2015

Parkinson's Disease

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“…D2 receptors are located both presynaptically (predominantly D2 S ), where they can inhibit dopamine release by decreasing calcium activity, and postsynaptically (predominantly D2 L ), where they can activate potassium channels [39, [124][125][126][127][128]. Immunohistochemical studies have demonstrated that the D4 receptor is found mainly (postsynaptically) in dendritic shafts and spines of mammalian striatum [108] and, by projecting back to the substantia nigra, may control dopaminergic transmission.…”

Section: Physiological Role Of the D4 Receptor In The Brainmentioning

confidence: 99%

The dopamine D4 receptor: biochemical and signalling properties

Rondou

Haegeman

Craenenbroeck

2010

Cell. Mol. Life Sci.

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Dopamine is an important neurotransmitter that regulates several key functions in the brain, such as motor output, motivation and reward, learning and memory, and endocrine regulation. Dopamine does not mediate fast synaptic transmission, but rather modulates it by triggering slow-acting effects through the activation of dopamine receptors, which belong to the G-protein-coupled receptor superfamily. Besides activating different effectors through G-protein coupling, dopamine receptors also signal through interaction with a variety of proteins, collectively termed dopamine receptor-interacting proteins. We focus on the dopamine D4 receptor, which contains an important polymorphism in its third intracellular loop. This polymorphism has been the subject of numerous studies investigating links with several brain disorders, such as attention-deficit hyperactivity disorder and schizophrenia. We provide an overview of the structure, signalling properties and regulation of dopamine D4 receptors, and briefly discuss their physiological and pathophysiological role in the brain.

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“…Mirtazapine exerts a complex interaction with several receptors, including indirect central nervous system 5-HT 1A agonism, 5-HT 2 antagonism, 5-HT 2C inverse agonism, 5-HT 3 antagonism, alpha-2 antagonism, and H 1 inverse agonism. 31 Several case reports have observed gastroparesis symptom reductions with open-label mirtazapine. In an initial report, mirtazapine 15 mg decreased emesis and allowed discontinuation of metoclopramide and lorazepam for 3 months in a 27-year-old diabetic with gastroparesis.…”

Section: Haslermentioning

confidence: 99%

Symptomatic Management for Gastroparesis

Hasler

2015

Gastroenterology Clinics of North America

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Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents

Cited by 67 publications

References 15 publications

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Monoamine Reuptake Inhibitors in Parkinson’s Disease

The dopamine D4 receptor: biochemical and signalling properties

Symptomatic Management for Gastroparesis

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