Synthesis and 5-HT2A Antagonist Activity of Derivatives of the Novel Heterocycles Indolo[3,2-d]pyrrolo[3,2-g]azecine and Benzo[d]pyrrolo[3,2-g]azecine compared to the Benz[d]indolo[2,3-g]azecine Derivative LE 300

Rostom, Sherif A. F.; Farghaly, A. M.; Soliman, F. S. G.; El-Semary, Mona M.; Elz, Sigurd; Lehmann, Jochen

doi:10.1002/1521-4184(200107)334:7<241::aid-ardp241>3.0.co;2-b

Cited by 17 publications

(3 citation statements)

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“…Ketanserin is a 5‐HT 2A/2C receptor antagonist (Hartman and Northup, 1996). In addition, the demonstrated affinities of LE300 and haloperidol to 5‐HT 2A receptors (Fontenla et al ., 1994; Seeman and Van Tol, 1994; Witt et al ., 2000; Rostom et al ., 2001; El‐Subbagh et al ., 2002) suggest that 5‐HT released by methamphetamine inhibits MSR via 5‐HT 2A receptors.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D₁‐like receptors in neonatal rats

Kawamoto¹,

Otsuguro²,

Ishizuka

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSEDopamine released from the endings of descending dopaminergic nerve fibres in the spinal cord may be involved in modulating functions such as locomotion and nociception. Here, we examined the effects of dopamine on spinal synaptic transmissions in rats. EXPERIMENTAL APPROACHSpinal reflex potentials, monosynaptic reflex potential (MSR) and slow ventral root potential (sVRP), were measured in the isolated spinal cord of the neonatal rat. Dopamine release was measured by HPLC. KEY RESULTSDopamine at lower concentrations (<1 mM) depressed sVRP, which is a C fibre-evoked polysynaptic response and believed to reflect nociceptive transmission. At higher concentrations (>1 mM), in addition to a potent sVRP depression, dopamine depolarized baseline potential and slightly depressed MSR. Depression of sVRP by dopamine was partially reversed by dopamine D1-like but not by D2-like receptor antagonists. SKF83959 and SKF81297, D1-like receptor agonists, and methamphetamine, an endogenous dopamine releaser, also caused the inhibition of sVRP. Methamphetamine also depressed MSR, which was inhibited by ketanserin, a 5-HT2A/2C receptor antagonist. Methamphetamine induced the release of dopamine and 5-HT from spinal cords, indicating that the release of endogenous dopamine and 5-HT depresses sVRP and MSR respectively. CONCLUSION AND IMPLICATIONSThese results suggested that dopamine at lower concentrations preferentially inhibited sVRP, which is mediated via dopamine D1-like and other unidentified receptors. The dopamine-evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways. AbbreviationsACSF, artificial cerebrospinal fluid; DRG, dorsal root ganglion; MSR, monosynaptic reflex potential; sVRP, slow ventral root potential IntroductionDopamine is a neurotransmitter in the CNS. Dopamine receptors are classified into five subtypes, referred to as either D1-like (D1 and D5) or D2-like (D2, D3 and D4) receptors (Missale et al., 1998; receptor nomenclature follows Alexander et al. 2011). Dopamine concentration is a key factor in the activation of different receptor subtypes. In the prefrontal cortex, low concentrations of dopamine act on D1-like receptors, while higher concentrations act on D2-like receptors (Zheng et al., 1999;Trantham-Davidson et al., 2004).BJP British Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2011 788 In the spinal cord, the descending dopaminergic fibre projects from the hypothalamic A11 region (Björklund and Skagerberg, 1979;Skagerberg and Lindvall, 1985;Millan, 2002;Benarroch, 2008), and dopamine can modulate locomotion and nociception (Clemens and Hochman, 2004;Han et al., 2007;Lapointe et al., 2009). In the rat spinal cord, dopamine at concentrations greater than 10 mM activates K + channels, producing hyperpolarization via D2-like receptors, but not D1-like receptors in substantia gelatinosa neurones, which are located in the superficial laminae of the dorsal horn receiving nociceptive inputs (Tamae et al., 2005;Taniguchi...

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Section: Discussionmentioning

confidence: 99%

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D₁‐like receptors in neonatal rats

Kawamoto¹,

Otsuguro²,

Ishizuka

et al. 2012

British J Pharmacology

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“…LE 300 is a hybrid of tryptamine and phenethylamine linked through the semi-rigid azecine ring, and showed a subnanomolar affinity towards the rat striatal D 1 receptor [9] and high functional activity at the 5-HT 2A receptor [10]. In the present study, some new analogs of LE 300 were synthesized from which the indole moiety was omitted, in order to estimate its necessity for biological activity.…”

Section: Introductionmentioning

confidence: 99%

Dopamine/Serotonin Receptor Ligands. Part IV [1]: Synthesis and Pharmacology of Novel 3-Benzazecines and 3-Benzazonines as Potential 5-HT2A and Dopamine Receptor Ligands

El‐Subbagh¹,

Wittig²,

Decker³

et al. 2002

Arch. Pharm. Pharm. Med. Chem.

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“…β-Carboline is a key pharmacophore present in a large number of natural tricyclic alkaloids, which can be found in numerous plants and animals, exhibiting potent biological activities [1,2,3,4,5,6,7,8,9,10]. As a key member of the β-carboline family, its structural variant tricyclic β-carbolinone (9 H -pyrido[3,4- b ]indol-1(2 H )-one derivative or β-carbolin-1-one, Figure 1) has served as an important intermediate for the preparation of complex alkaloids [11,12,13,14,15,16,17,18,19] and has been found to possess potent bioactivities. The natural and synthetic β-carbolinones are reported to have pharmacological effects in several aspects, such as the anticancer activity against colon and lung cancers, central nervous system activity in mammals, and also as the biological control agent for receptor research on bio-enzyme inhibitors, such as the inhibition of HLE (Human leukocyte elastase) [20,21,22,23].…”

Section: Introductionmentioning

confidence: 99%

A Facile Synthesis of 3-Substituted 9H-Pyrido[3,4-b]indol-1(2H)-one Derivatives from 3-Substituted β-Carbolines

et al. 2010

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A mild and efficient two-step synthesis of 3-substituted β-carbolinone derivatives from 3-substituted β-carboline in good yields is described. A possible reaction mechanism for the formation of the skeleton of β-carbolin-1-one is proposed. The structures of these compounds were established by IR, 1H-NMR, 13C-NMR, mass spectrometry and elemental analysis, as well as X-ray crystallographic analysis of 4-2 and 6-2.

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Synthesis and 5-HT2A Antagonist Activity of Derivatives of the Novel Heterocycles Indolo[3,2-d]pyrrolo[3,2-g]azecine and Benzo[d]pyrrolo[3,2-g]azecine compared to the Benz[d]indolo[2,3-g]azecine Derivative LE 300

Cited by 17 publications

References 20 publications

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D₁‐like receptors in neonatal rats

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D₁‐like receptors in neonatal rats

Dopamine/Serotonin Receptor Ligands. Part IV [1]: Synthesis and Pharmacology of Novel 3-Benzazecines and 3-Benzazonines as Potential 5-HT2A and Dopamine Receptor Ligands

A Facile Synthesis of 3-Substituted 9H-Pyrido[3,4-b]indol-1(2H)-one Derivatives from 3-Substituted β-Carbolines

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Synthesis and 5-HT2A Antagonist Activity of Derivatives of the Novel Heterocycles Indolo[3,2-d]pyrrolo[3,2-g]azecine and Benzo[d]pyrrolo[3,2-g]azecine compared to the Benz[d]indolo[2,3-g]azecine Derivative LE 300

Cited by 17 publications

References 20 publications

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D1‐like receptors in neonatal rats

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D1‐like receptors in neonatal rats

Dopamine/Serotonin Receptor Ligands. Part IV [1]: Synthesis and Pharmacology of Novel 3-Benzazecines and 3-Benzazonines as Potential 5-HT2A and Dopamine Receptor Ligands

A Facile Synthesis of 3-Substituted 9H-Pyrido[3,4-b]indol-1(2H)-one Derivatives from 3-Substituted β-Carbolines

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Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D₁‐like receptors in neonatal rats

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D₁‐like receptors in neonatal rats