Circling behaviour induced by dopamine releasers and/or uptake inhibitors during degeneration of the nigrostriatal pathway

Oberlander, Claude; Euvrard, C.; Dumont, C; Boissier, Jacques R.

doi:10.1016/0014-2999(79)90215-2

Cited by 35 publications

(8 citation statements)

References 20 publications

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“…Both of these motor behaviors are recognized as lines of evidence supportive of central dopaminergic stimulation in 6-OHDA model of PD. [79][80][81][82] We found that injection of compound 10 into 6-OHDA-lesioned mice produced statistically significant increases in forward locomotion at each measured time interval (Figure 14A) and in the total distance traveled during the observation period (Figure 14B), compared to the vehicle control. Similar effects were observed in mice that were administered SKF81297.…”

Section: Behavioral Studies In Micementioning

confidence: 90%

Designing Functionally Selective Noncatechol Dopamine D₁ Receptor Agonists with Potent In Vivo Antiparkinsonian Activity

Martini

Ray

et al. 2019

ACS Chem. Neurosci.

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Dopamine receptors are important G protein-coupled receptors (GPCRs) with therapeutic opportunities for treating Parkinson’s Disease (PD) motor and cognitive deficits. Biased D1 dopamine ligands that differentially activate G protein over β-arrestin recruitment pathways are valuable chemical tools for dissecting positive versus negative effects in drugs for PD. Here, we reveal an iterative approach toward modification of a D1-selective noncatechol scaffold critical for G protein-biased agonism. This approach provided enhanced understanding of the structural components critical for activity and signaling bias and led to the discovery of several novel compounds with useful pharmacological properties, including three highly GS-biased partial agonists. Administration of a potent, balanced, and brain-penetrant lead compound from this series results in robust antiparkinsonian effects in a rodent model of PD. This study suggests that the noncatechol ligands developed through this approach are valuable tools for probing D1 receptor signaling biology and biased agonism in models of neurologic disease.

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Section: Behavioral Studies In Micementioning

confidence: 90%

Designing Functionally Selective Noncatechol Dopamine D₁ Receptor Agonists with Potent In Vivo Antiparkinsonian Activity

Martini

Ray

et al. 2019

ACS Chem. Neurosci.

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“…Pharmacological studies of BZP showed a central serotoninomimetic action, which involves serotonin (5-HT) uptake inhibition and 5-HT 1 receptor agonistic effects [83]. Furthermore, weak inhibition of serotonin transporters, noradrenaline release and interactions with the dopaminergic system were described [84][85][86][87]. Studies with healthy volunteers corroborated the amphetamine-like effects also in vivo [88] and a double blind study with former amphetamine addicts showed that BZP and amphetamine produced indistinguishable subjective effects [89].…”

Section: N-benzylpiperazine (Bzp)mentioning

confidence: 99%

Metabolism of Designer Drugs of Abuse

Staack

Maurer

2005

CDM

107

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Abuse of designer drugs is widespread among young people, especially in the so-called "dance club scene" or "rave scene", worldwide. Severe and even fatal poisonings have been attributed to the consumption of such drugs of abuse. However, in contrast to new medicaments, which are extensively studied in controlled clinical studies concerning metabolism, including cytochrome P450 isoenzyme differentiation, and further pharmacokinetics, designer drugs are consumed without any safety testing. This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4-methylthioamphetamine (4-MTA), were taken into consideration as new "classical" amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3, 4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) were taken into consideration as derivatives of the class of piperazine-derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha-pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing identification of in vivo or in vitro human or animal metabolites and cytochrome P450 isoenzyme dependent metabolism have been considered and summarized.

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“…With the majority of dopaminergic neurons in mammals innervating the midbrain (Vitalis et al, 2005), dopaminergic signaling modulates a wide array of behaviors (e.g. motor activity, stereotypy; Ungerstedt, 1976, Oberlander et al, 1979). Impaired dopaminergic signaling can lead to behavioral pathologies such as Parkinson’s disease, schizophrenia, and attention deficit hyperactivity disorder (Hirsch, 1992, Cortese et al, 2005, Zeiss, 2005, Bowton et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Acute administration of dopaminergic drugs has differential effects on locomotion in larval zebrafish

Irons

Kelly

Hunter

et al. 2013

Pharmacology Biochemistry and Behavior

147

130

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Altered dopaminergic signaling causes behavioral changes in mammals. In general, dopaminergic receptor agonists increase locomotor activity, while antagonists decrease locomotor activity. In order to determine if zebrafish (a model organism becoming popular in pharmacology and toxicology) respond similarly, the acute effects of drugs known to target dopaminergic receptors in mammals were assessed in zebrafish larvae. Larvae were maintained in 96-well microtiter plates (1 larva/well). Non-lethal concentrations (0.2–50 µM) of dopaminergic agonists (apomorphine, SKF-38393, and quinpirole) and antagonists (butaclamol, SCH-23390, and haloperidol) were administered at 6 days post-fertilization (dpf). An initial experiment identified the time of peak effect of each drug (20–260 minutes post-dosing, depending on the drug). Locomotor activity was then assessed for 70 minutes in alternating light and dark at the time of peak effect for each drug to delineate dose-dependent effects. All drugs altered larval locomotion in a dose-dependent manner. Both the D1- and D2-like selective agonists (SKF-38393 and quinpirole, respectively) increased activity, while the selective antagonists (SCH-23390 and haloperidol, respectively) decreased activity. Both selective antagonists also blunted the response of the larvae to changes in lighting conditions at higher doses. The nonselective drugs had biphasic effects on locomotor activity: apomorphine increased activity at the low dose and at high doses, while butaclamol increased activity at low to intermediate doses, and decreased activity at high doses. This study demonstrates that (1) larval zebrafish locomotion can be altered by dopamine receptor agonists and antagonists, (2) receptor agonists and antagonists generally have opposite effects, and (3) drugs that target dopaminergic receptors in mammals appear, in general, to elicit similar locomotor responses in zebrafish larvae.

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Circling behaviour induced by dopamine releasers and/or uptake inhibitors during degeneration of the nigrostriatal pathway

Cited by 35 publications

References 20 publications

Designing Functionally Selective Noncatechol Dopamine D₁ Receptor Agonists with Potent In Vivo Antiparkinsonian Activity

Designing Functionally Selective Noncatechol Dopamine D₁ Receptor Agonists with Potent In Vivo Antiparkinsonian Activity

Metabolism of Designer Drugs of Abuse

Acute administration of dopaminergic drugs has differential effects on locomotion in larval zebrafish

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Circling behaviour induced by dopamine releasers and/or uptake inhibitors during degeneration of the nigrostriatal pathway

Cited by 35 publications

References 20 publications

Designing Functionally Selective Noncatechol Dopamine D1 Receptor Agonists with Potent In Vivo Antiparkinsonian Activity

Designing Functionally Selective Noncatechol Dopamine D1 Receptor Agonists with Potent In Vivo Antiparkinsonian Activity

Metabolism of Designer Drugs of Abuse

Acute administration of dopaminergic drugs has differential effects on locomotion in larval zebrafish

Contact Info

Product

Resources

About

Designing Functionally Selective Noncatechol Dopamine D₁ Receptor Agonists with Potent In Vivo Antiparkinsonian Activity

Designing Functionally Selective Noncatechol Dopamine D₁ Receptor Agonists with Potent In Vivo Antiparkinsonian Activity