Anti‐Obsessional and Antidepressant Profile of Besipirdine

Smith, Craig P.; Woods-Kettelberger, Ann T.; Corbett, Rebecca; Porsolt, Roger D.; Roehr, Joachim E.; Bores, Gina M.; Giovanni, Andrew; Szewczak, Mark R.; Rush, Douglas K.; Martin, Lawrence L.; Klein, Joseph; Turk, D. J.; DiLeo, Eva M.; Effland, Richard C.; Huger, Francis P.; Kongsamut, Sathapana

doi:10.1111/j.1527-3458.1997.tb00313.x

Cited by 7 publications

(5 citation statements)

References 63 publications

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“…Duloxetine, through inhibition of 5-HT and NE reuptakes, potentiates the glutamate excitatory neurotransmission to the SS. Therefore, although this anatomical structure has not been described in the rabbit until now, we hypothesize that besipirdine-induced potentiation of SS-EMG activity could be due to the inhibition of NE reuptake at a similar neuronal structure to the Onuf nucleus in the rabbit, since it was previously demonstrated that besipirdine easily penetrates the brain-blood barrier [12] .…”

Section: Discussionmentioning

confidence: 99%

“…This in vivo potency on NE reuptake is in keeping with results previously obtained, i.e. besipirdine at 2.5 mg/kg s.c. greatly increased the extracellular levels of NE over the controls in the hippocampus of awake rats [12] .…”

Section: Discussionmentioning

confidence: 99%

“…The doses of duloxetine and besipirdine were selected on the basis of pilot experiments and on previously published data on their relative efficacy when given systemically [1,4,12,16,17] .…”

Section: Cystometrymentioning

confidence: 99%

“…It previously failed to demonstrate efficacy in the treatment of Alzheimer´s disease [8] . Together with its metabolite, N-despropyl-besipirdine (HP-748), besipirdine mechanisms of action combines NE reuptake inhibition and activation of ␣ 1 -adrenoceptors [9][10][11][12] . It is a weak potassium and sodium channel blocker [10] and has a weak or nonappreciable binding affinity for several types of receptors such as 5-HT 1a , 5-HT 1b , 5-HT 2a , dopaminergics and M 3 muscarinic receptors [12,13] .…”

Section: Introductionmentioning

confidence: 99%

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Halothane-Anesthetized Rabbit: A New Experimental Model to Test the Effects of Besipirdine and Duloxetine on Lower Urinary Tract Function

Pérez-Martínez

Vela-Navarrete²,

Virseda³

et al. 2010

Urol Int

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Introduction: The effects of besipirdine and its main metabolite, HP-748, as well as duloxetine and tomoxetine in the lower urinary tract (LUT) were studied using in vitro and in vivo techniques. Materials and Methods: For in vivo studies, besipirdine or duloxetine effects on cystometric parameters and striated sphincter electromyographic (SS-EMG) activity were investigated. On the isolated urethra, norepinephrine (NE) concentration-response curves (CRC) were performed in the presence of besipirdine, duloxetine or tomoxetine. Moreover, CRC to HP-748 were constructed in the absence or presence of prazosin. Potency (pEC₅₀) and maximal responses (E_max) were determined. Results: Besipirdine at 1, 3 and 5 mg/kg intravenously (i.v.) induced a significant increase in SS-EMG activity (250, 273 and 241%, respectively), bladder capacity (172, 197, and 235%, respectively), intercontraction interval (ICI; 208, 242, and 400%, respectively), and residual volume (181, 191, and 236%, respectively). Duloxetine at 2 mg/kg i.v. increased significantly SS-EMG activity (219%), micturition volume (222%), and ICI (205%). In the isolated urethra, besipirdine, tomoxetine and duloxetine significantly displaced to the left the NE CRC. In addition, HP-748 induced contraction of the isolated urethra with a pEC₅₀ of 5.89 and an E_max of 37%. Conclusions: These data support the potential of besipirdine as a new drug for LUT dysfunctions such as stress and mixed urinary incontinence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cystometrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Halothane-Anesthetized Rabbit: A New Experimental Model to Test the Effects of Besipirdine and Duloxetine on Lower Urinary Tract Function

Pérez-Martínez

Vela-Navarrete²,

Virseda³

et al. 2010

Urol Int

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“…Heterocyclyluracils have been extensively studied in the development of novel pesticides as highly efficient herbicides . Besipirdine is believed to enhance both cholinergic and adrenergic neurotransmission in the central nervous system and release the syndromes caused by Alzheimer’s disease . Binedaline has been investigated in clinical trials as a candidate antidepressant drug with fewer side effects than conventional tricyclic antidepressants .…”

mentioning

confidence: 99%

Catalytic N-Acylation for Access to N–N Atropisomeric N-Aminoindoles: Choice of Acylation Reagents and Mechanistic Insights

Song,

Pang,

Deng

et al. 2024

ACS Catal.

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The synthesis of N−N axial compounds containing aromatic acyl amides using common acylation reagents remains challenging. We describe a highly atropenantioselective synthesis of N-aminoindoles containing N−N axes. A chiral cyclic isothiourea is used as the sole organic catalyst in the atropenantioselective transformation of the N-acylation reaction. Aroyl chlorides have been used as acylation reagents to construct atropisomeric compounds through N-acylation. The N-aminoindole products, which bear stereogenic N−N axes, were synthesized with high yields and enantioselectivities. Some of the enantiopure Naminoindole products exhibited promising antibacterial activities against plant pathogens.

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Neurobiology and Pharmacotherapy of Obsessive‐Compulsive Disorder

Rapoport

Inoff‐Germain

2007

Handbook of Contemporary Neuropharmacology

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Obsessive‐compulsive disorder (OCD) is characterized by the presence of unwanted, senseless, intrusive and distressing thoughts, urges and images (obsessions) and/or repetitive behaviors (compulsions). While classified as an anxiety disorder in DSM‐IV, OCD is given a separate chapter here as the clinical phenomenology, drug treatment response, family studies, and brain imaging data support a separate neurobiological classification for this disorder and a distinct neuropharmacologic profile as well. Our current understanding of its underlying neurobiology as well as the state of treatment for OCD is provided through a selective review of OCD‐related (1) brain imaging studies, (2) genetic studies, (3) animal models, (4) psychopharmacology, including immunomodulatory treatment, and (5) experimental non‐pharmacological treatments such as neurosurgery, transcranial magnetic stimulation, and deep brain stimulation.

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Anti‐Obsessional and Antidepressant Profile of Besipirdine

Cited by 7 publications

References 63 publications

Halothane-Anesthetized Rabbit: A New Experimental Model to Test the Effects of Besipirdine and Duloxetine on Lower Urinary Tract Function

Halothane-Anesthetized Rabbit: A New Experimental Model to Test the Effects of Besipirdine and Duloxetine on Lower Urinary Tract Function

Catalytic N-Acylation for Access to N–N Atropisomeric N-Aminoindoles: Choice of Acylation Reagents and Mechanistic Insights

Neurobiology and Pharmacotherapy of Obsessive‐Compulsive Disorder

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