N-{[1-(2-Phenylethyl)pyrrolidin-2-yl]methyl}cyclohexane-carboxamides as selective 5-HT1A receptor agonists

Fujio, Masakazu; Togo, Yoshifumi; Tomozane, Hideo; Kuroita, Takanobu; Morio, Yasunori; Katayama, Jiro; Matsumoto, Yasuhiro

doi:10.1016/s0960-894x(00)00030-5

Cited by 10 publications

(4 citation statements)

References 13 publications

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“…An example of such a drug is 8-OH-DPAT (the binding of related 7-OH-DPAT is mentioned above), which is used in the tritiated form as a radioligand for 5-HT receptors. [ 3 H]8-OH-DPAT binds to 5-HT 1A receptors with high affinity (pK i = 9.33 [ 131 ]). The affinity of 5-HT 1B receptors is lower (pK i = 6.25 [ 132 ]) and corresponds to the affinity to DR (pK i = 7.07 [ 133 ]).…”

Section: Discussionmentioning

confidence: 99%

Dopamine and Dopamine-Related Ligands Can Bind Not Only to Dopamine Receptors

Mysliveček

2022

Life

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The dopaminergic system is one of the most important neurotransmitter systems in the central nervous system (CNS). It acts mainly by activation of the D1-like receptor family at the target cell. Additionally, fine-tuning of the signal is achieved via pre-synaptic modulation by the D2-like receptor family. Some dopamine drugs (both agonists and antagonists) bind in addition to DRs also to α2-ARs and 5-HT receptors. Unfortunately, these compounds are often considered subtype(s) specific. Thus, it is important to consider the presence of these receptor subtypes in specific CNS areas as the function virtually elicited by one receptor type could be an effect of other—or the co-effect of multiple receptors. However, there are enough molecules with adequate specificity. In this review, we want to give an overview of the most common off-targets for established dopamine receptor ligands. To give an overall picture, we included a discussion on subtype selectivity. Molecules used as antipsychotic drugs are reviewed too. Therefore, we will summarize reported affinities and give an outline of molecules sufficiently specific for one or more subtypes (i.e., for subfamily), the presence of DR, α2-ARs, and 5-HT receptors in CNS areas, which could help avoid ambiguous results.

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Section: Discussionmentioning

confidence: 99%

Dopamine and Dopamine-Related Ligands Can Bind Not Only to Dopamine Receptors

Mysliveček

2022

Life

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“…Besides the efforts to develop long-chain arylpiperazine derivatives, (S)-PPMMB with a completely different chemical structure was generated as a novel agonist of the 5-HT 1A receptors, which had high affinity (K i = 4.3 nM) and high selectivity. 181 Subsequently, biodistribution and ex vivo autoradiograms in rats showed that [ 11 C](S)-PPMMB ([ 11 C]51, Figure 7) could readily penetrate the BBB yet with a homogeneous distribution in different brain regions. 182 Further blocking experiments were carried out in ex vivo ARG with WAY-100635 and 8-OH-DPAT, and the results revealed that the uptake of [ 11 C]51 was not reduced in any of the brain regions.…”

Section: Nm [ 3 H]dtg Assay)mentioning

confidence: 99%

“…However, the radioactivity was cleared rapidly from the whole brain to the same level as that of the cerebellum after 40 min postinjection, indicating its limited binding with the 5-HT 1A receptors in vivo. Besides the efforts to develop long-chain arylpiperazine derivatives, ( S )-PPMMB with a completely different chemical structure was generated as a novel agonist of the 5-HT 1A receptors, which had high affinity ( K i = 4.3 nM) and high selectivity . Subsequently, biodistribution and ex vivo autoradiograms in rats showed that [ 11 C]( S )-PPMMB ([ 11 C] 51 , Figure ) could readily penetrate the BBB yet with a homogeneous distribution in different brain regions .…”

Section: Pet Ligands For 5-ht1a Receptorsmentioning

confidence: 99%

Positron Emission Tomography (PET) Imaging Tracers for Serotonin Receptors

Rong

Chen

et al. 2022

J. Med. Chem.

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Serotonin (5-hydroxytryptamine, 5-HT) and 5-HT receptors (5-HTRs) have crucial roles in various neuropsychiatric disorders and neurodegenerative diseases, making them attractive diagnostic and therapeutic targets. Positron emission tomography (PET) is a noninvasive nuclear molecular imaging technique and is an essential tool in clinical diagnosis and drug discovery. In this context, numerous PET ligands have been developed for "visualizing" 5-HTRs in the brain and translated into human use to study disease mechanisms and/or support drug development. Herein, we present a comprehensive repertoire of 5-HTR PET ligands by focusing on their chemotypes and performance in PET imaging studies. Furthermore, this Perspective summarizes recent 5-HTR-focused drug discovery, including biased agonists and allosteric modulators, which would stimulate the development of more potent and subtype-selective 5-HTR PET ligands and thus further our understanding of 5-HTR biology.

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“…11 As a consequence, it is difficult to discover a selective 5-HT 1A receptor agonist over dopamine D 2 and a 1 -adrenergic receptors and many researchers around the world have been working on this issue. [12][13][14] We have also reported 1,4-benzoxazepine (1,4-BZO) derivatives which are selective 5-HT 1A receptor agonists with potent anti-ischemic effects. 15 In order to improve affinity and selectivity for the 5-HT 1A receptor, we have attempted to modify amine moiety of 1,4-BZO derivatives.…”

Section: Introductionmentioning

confidence: 99%