SCH-23390 / Boehringer Ingelheim - LARVOL DELTA

GABAB receptors negatively modulate excitatory plasticity at the mossy fiber synapse onto parvalbumin-expressing basket and axo-axonic cells in the dentate gyrus. (PubMed, Front Synaptic Neurosci) - "Finally, pre-application of SCH-23390, a blocker of Kir3 channels, occluded the inhibitory effect of baclofen on LTP. These results demonstrate that postsynaptic GABABRs negatively regulate synaptic plasticity at MF synapses onto DG perisomatic-inhibitory PV-INs via Kir3 channels."

Journal

Exploration of neural mechanisms underlying antidepressant-like property of Ziziphora clinopodioides Lam. essential oil using mouse forced swimming test: Involvement of the monoaminergic systems. (PubMed, Curr Res Physiol) - "Moreover, naloxone (non-selective antagonist for opioid receptor subtypes, 1 mg/kg), prazosin (α1-adrenergic receptor antagonist, 1 mg/kg), yohimbine (α2-adrenergic receptor antagonist, 1 mg/kg), propranolol (β-adrenergic receptor antagonist, 2 mg/kg), WAY100635 (selective 5-HT1A receptor antagonist, 0.1 mg/kg), ondansetron (5-HT3 receptor antagonist, 1 mg/kg), haloperidol (non-selective dopamine receptor blocker, 0.2 mg/kg), SCH23390 (selective dopamine D1 receptor blocker, 0.05 mg/kg), sulpiride (selective dopamine D2 receptor blocker, 50 mg/kg) and flumazenil (GABAA/BDZ receptor antagonist, 10 mg/kg) were used to ascertain the neural pathways implicated in the antidepressant-like response of EOZC. However, this effect remained unaffected by naloxone, propranolol and flumazenil. These findings indicate that EOZC elicits antidepressant-like response, which relies on its interaction with noradrenergic, serotonergic and..."

Journal • Preclinical • Addiction (Opioid and Alcohol) • DRD2

ECHINATIN AS A MULTIMODAL MODULATOR OF MONOAMINERGIC SYSTEM: PRECLINICAL EVIDENCE FOR ANTIDEPRESSANT-LIKE ACTIVITY. (PubMed, Eur J Pharmacol) - "Male BALB/c mice received echinatin (20 or 30 mg/kg), fluoxetine (10 mg/kg) or reboxetine (20 mg/kg). The anti-immobility effect was abolished by serotonergic (PCPA, WAY-100635), noradrenergic (AMPT, phentolamine, propranolol) and dopaminergic (SCH-23390, sulpiride) interventions, but was not altered by ketanserin. These findings provide the first pharmacological evidence that echinatin elicits antidepressant-like effects through broad monoaminergic modulation and support its further evaluation as a potential lead compound for antidepressant drug development."

Journal • Preclinical • CNS Disorders • Mood Disorders • Psychiatry

Peptide IRW upregulates ACE2 in spontaneously hypertensive rats via dopamine/D1R signaling pathway. (PubMed, J Adv Res) - "IRW-driven ACE2 upregulation in vivo relies on the dopamine/D1R signaling pathway, highlighting the therapeutic potential of this pathway for ACE2-related conditions."

Journal • Preclinical • ACE2 • NR4A1

Central injection of epidermal growth factor (EGF) induces hypophagia via D₁ dopaminergic and β₂ adrenergic receptors in broiler chickens. (PubMed, Poult Sci) - "Experiments 2-10 evaluated the effects of co-injection of EGF (200 ng) with various pharmacological agents and receptor antagonists: SCH23390 (D₁-dopaminergic), AMI-193 (D₂-dopaminergic), l-DOPA (dopamine precursor), 6-OHDA (dopaminergic neurotoxin), prazosin (α₁-adrenergic), yohimbine (α₂-adrenergic), metoprolol (β₁-adrenergic), ICI 118,551 (β₂-adrenergic), and SR 59230R (β₃-adrenergic). Antagonists for α₁, α₂, β₁, and β₃ adrenergic receptors, as well as D₂ dopaminergic receptors, had no significant effect on EGF-induced anorexia (P ≥ 0.05). These findings demonstrate, for the first time, that central EGF acts as an appetite-suppressing peptide in broilers, and its effect is specifically mediated through interactions with D₁ dopaminergic and β₂ adrenergic receptor systems."

Journal • Anorexia

Effect of dopamine on TGF-β2 secretion by human retinal pigment epithelial cells and the underlying mechanism. (PubMed, PLoS One) - "Our findings suggest that dopamine suppresses TGF-β2 secretion in human retinal pigment epithelial cells primarily through activation of D2 receptors, which appears to involve the YAP-TGF-β-Smad signaling pathway. This regulatory mechanism may contribute to the control of scleral remodeling and thus influence the development of myopia."

Journal • Ophthalmology • DRD1 • DRD2 • SMAD7 • TGFB1

Reducing stress and alcohol-related behaviors by targeting D1-CRHR1 receptor interactions in the amygdala. (PubMed, Front Pharmacol) - "We then injected stressin I (0.01 μg/0.5 μL) and stressin I in combination with the D1 antagonist SCH23390 (120 ng/0.5 μL) site-specifically into the ITC and tested animals in the Elevated-Plus-Maze (EPM), followed by saturated D1 receptor autoradiography...Our immunohistochemical findings also suggest the D1-CRHR1 interaction is dependent on co-localized receptors. Our findings suggest D1-CRHR1 interactions within the ITC of the amygdala in response to stress, alcohol behavior, and the development of dependence, thereby providing a novel mechanism that may be targetable by therapeutic polypharmacological interference."

Journal • Addiction (Opioid and Alcohol) • Mood Disorders • Psychiatry

Central administration of C-type natriuretic peptide (CNP) modulates food consumption in broilers: involvement of dopaminergic, melanocortinergic, and neuropeptide Y receptors. (PubMed, Vet Res Commun) - "However, simultaneous infusion of 6-OHDA, SCH23390, and SHU9119 with CNP-22 markedly decreased CNP-22-induced anorexia (P < 0.05). The data indicate that CNP-22 administration suppresses feeding behavior in young broiler chickens, a process potentially mediated via the D1, MC3/MC4, and NPY1 receptors pathways."

Journal • Anorexia • DRD2

Central kisspeptin injection enhances food consumption in broiler chickens: role of opioidergic and dopaminergic receptors. (PubMed, Poult Sci) - "However, simultaneous infusion of β-FNA and SCH 23390 with kisspeptin markedly increased kisspeptin-stimulated hyperphagia (P < 0.05). The data indicate that kisspeptin promotes hyperphagia in neonatal broiler-type chickens, and the hyperphagic response is mediated through mu-opioid and D1-dopaminergic receptor pathways."

Journal • Addiction (Opioid and Alcohol)

Methylphenidate Inhibits the Development of Myopia by Altering Dopamine and Norepinephrine Reuptake. (PubMed, Invest Ophthalmol Vis Sci) - "DA and NE receptors were pharmacologically blocked (DA = spiperone, SCH-23390; and NE = yohimbine) to determine their role in MPH's anti-myopic effects. MPH suppresses experimental myopia, with its effects linked to increased extracellular levels of DA and NE. These findings align with the anti-myopic effects observed in clinical studies, supporting a role for DA in human myopia and suggesting that NE may also contribute to the regulation of ocular growth."

Journal • Ophthalmology

D1-like dopamine receptors in the dentate gyrus mediate cannabidiol's facilitation of extinction and prevention of reinstatement in methamphetamine-induced conditioned place preference. (PubMed, Pharmacol Biochem Behav) - "Methamphetamine (METH) is a highly addictive psychostimulant, and despite its widespread abuse, there are no FDA-approved treatments for METH use disorder (MUD). Moreover, SCH23390 (1 and 4 μg) reversed CBD's prevention of reinstatement of METH-CPP. These findings suggest that D1Rs in the DG region are involved in mediating CBD's effects and offer insights into its therapeutic potential for MUD."

Journal

Clustering Cortical Rhythms: Monoaminergic Signatures in Time-Frequency EEG Dynamics. (PubMed, Biomedicines) - " We looked at how the EEG effects of serotonin, dopamine, and norepinephrine receptors activating substances (quipazine, SKF-38393, and clonidine, respectively) injected into the brain's lateral ventricles were affected by corresponding blockers (cyproheptadine, SCH-23390, and yohimbine) in freely moving rats. These results demonstrate the "signatures" of different MA systems in EEG time-frequency clustering. We consider the developed approach as a potentially useful tool in clinics for evaluation of MA transmission pathology and its therapy with corresponding substances penetrating the blood-brain barrier."

Journal • CNS Disorders

Dopamine inhibits excitatory synaptic responses in layer I of the rat parasubiculum. (PubMed, Neurosci Lett) - "Application of the dopamine D1-like receptor antagonist SCH23390 failed to block the reduction in fEPSP amplitude induced by dopamine, but the D2-like receptor antagonist sulpiride prevented significant reductions in fEPSPs. Application of sulpiride alone facilitated fEPSP amplitude to 110 ± 3 % of baseline. These findings suggest that strong activation of dopaminergic inputs to the parasubiculum likely results in reduced excitatory synaptic activation of parasubicular neurons which may attenuate activity in their outputs to the entorhinal cortex."

Journal • Preclinical

Fiber Photometry Analysis of Spontaneous Dopamine Signals: The Z-Scored Data Are Not the Data. (PubMed, ACS Chem Neurosci) - "The D1-like receptor antagonist SCH23390 was used to prevent dLight sensors from interacting with dopamine in the extracellular space, while cocaine was used to inhibit uptake and raclopride to increase the release of dopamine...Finally, raclopride-induced increases in amplitude were correctly identified by all three methods, but this effect was again diminished by using the Z-score method. Thus, analysis of spontaneous dopamine signals requires assessment of the %ΔF/F values, and the use of z-scoring is not appropriate."

Journal

Role of ventromedial hypothalamic dopaminergic D1-like receptors in regulating standard food intake in 24-hour food-deprived male rats. (PubMed, Brain Res) - "Using selective intra-VMH D1-like receptor activation via SKF38393 and antagonism via SCH23390, we assessed the effects of VMH dopamine D1-like receptors on food consumption...In addition, we determined that this response was independent of locomotor activity. The study advances our understanding of hypothalamic dopamine pathways in appetite regulation, highlighting VMH D1-like receptors as a potential target for interventions in metabolic disorders."

Journal • Preclinical • Metabolic Disorders

Hunger By Proxy: Social Influence On Food Intake In Mice Via Dopamine Signaling (ENDO 2025) - "In a follow-up experiment, Group B mice received intraperitoneal injections of either 0.1 ml of 0.9% saline, a D1 dopamine receptor (DRD1) inhibitor (SCH23390, 0.1 mg/kg), or a D2 dopamine receptor (DRD2) inhibitor (Eticlopride, 1 mg/kg) 15 minutes before testing, and food intake was measured... Our findings confirm that social observation influences food intake in mice, but only for palatable foods such as sucrose diet. Dopamine signaling appears to regulate, or at least partially mediate, this hunger transmission effect. Establishing this animal model provides a foundation for future studies on the neurobiological mechanisms underlying cognitive-driven food intake and may contribute to the development of targeted therapeutic strategies for obesity."

Late-breaking abstract • Preclinical • Genetic Disorders • Obesity • DRD2

Knockout of Bmal1 in dopaminergic neurons induces ADHD-like symptoms via hyperactive dopamine signaling in male mice. (PubMed, Behav Brain Funct) - "This study finds that BMAL1 ablation in dopaminergic neurons induces ADHD-like phenotypes in male mice, identifying hyperactive dopamine signaling as a potential mediator of these phenotypes. It unveils a novel role for BMAL1 in regulating dopamine signaling and provide insights into circadian gene-driven psychiatric pathophysiology."

Journal • Preclinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Mental Retardation • Psychiatry • ARNTL • BMAL1

NMDA current is enhanced by MβCD-induced D1-NMDA receptor perturbation in hippocampal CA1. (PubMed, Neurosci Lett) - "Moreover, CaMKII inhibitory peptide 281-309 significantly counteracted the increased synaptic response observed in SCH23390 + MβCD conditions. Together, these results support the notion that lipid rafts perturbation impedes a NMDARs-D1Rs interaction, therefore a modulatory inhibition depending on this interaction."

Journal

Using cocaine and apomorphine self-administration in rats to measure the pharmacokinetics of competitive dopamine receptor antagonists administered by different routes. (PubMed, Sci Rep) - "This study investigated the time course and magnitude of effect of the D1- and D2- selective antagonists, SCH23390 and (-)Eticlopride respectively, on cocaine and apomorphine self-administration when administered via intravenous, subcutaneous, and intraperitoneal routes...Cocaine and apomorphine self-administration in rats can be used as a pharmacological bioassay system to measure the pharmacokinetics of dopamine receptor antagonists, presumably in the brain, in real time in-vivo. This assay system may provide pharmacokinetic information complimentary to standard timed plasma concentration methods."

Journal • PK/PD data • Preclinical

N-acetyltransferase 10 in the nucleus accumbens participates in methamphetamine-induced conditioned place preference and hyperlocomotion in mice. (PubMed, Neurochem Int) - "Using intraperitoneal administration of 0.1 mg/kg SCH23390, a dopamine D1 receptor (D1R) antagonist, we found that D1R antagonism significantly suppressed the METH-induced upregulation of NAT10 in the NAc and inhibited hyperlocomotion. AAV-shNAT10 also inhibited METH-induced upregulation of PSD95 and preserved dendritic morphology in the NAc. These findings suggest that NAT10 contributes to the development of METH-induced reward-related behaviors by modulating dendritic plasticity in the NAc."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Depression • Mood Disorders • Psychiatry • Substance Abuse • DLG4 • NAT10

Nitrous oxide exerts rewarding effect via regulating D1 receptor and BDNF pathway in ventral tegmental area-nucleus accumbens dopamine circuit (CINP-AsCNP 2025) - "This was abrogated by microinjection into the nucleus accumbens (NAc) of the dopamine (DA) D1 receptor antagonist SCH23390, but not the D2 antagonist haloperidol. These results indicate that the rewarding properties of N2O at subanesthetic concentration are associated with its upregulation of the VTA-NAc DA reward pathway probably via mediation of D1 receptor and BDNF/TrkB signaling. Among them, the modulation of BDNF may be the upstream of D1 receptor involved in N2O rewarding effect."

Anesthesia • CNS Disorders • Pain • Psychiatry • BDNF

Light Inhibits Lens-Induced Myopia through an Intensity-Dependent Dopaminergic Mechanism. (PubMed, Ophthalmol Sci) - "In a separate experiment, a D1-like (SCH-23390) or D2-like (spiperone) receptor antagonist was administered (once daily) to chicks wearing negative lenses under 40 000 lux (n = 5 to 6 per group) for a period of 5 days...These differences are most likely linked to the presence of a defocus-driven end point for growth in LIM that is not present in FDM. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Journal • Ophthalmology

Apomorphine-induced disruption of paced mating behavior in female rats is attenuated by eticlopride, a D2 receptor antagonist, but not SCH 23390, a D1 receptor antagonist. (PubMed, Horm Behav) - "Effects of apomorphine were not altered by SCH 23390 pretreatment. Apomorphine only affects sexual motivation when mating is possible, indicating that dopamine manipulation influences the physiology that supports behavioral response to sexual stimulation."

Journal • Preclinical

D2 receptor activation modulates NMDA receptor antagonist-enhanced high-frequency oscillations in the olfactory bulb of freely moving rats. (PubMed, Psychopharmacology (Berl)) - "These results suggest that NMDA receptor antagonist-enhanced HFO in the OB is generated predominantly independently of DA influence, however exogenous stimulation of D2R can modulate this rhythm. A second, but not third generation antipsychotic reduced HFO frequency."

Journal • Preclinical • CNS Disorders • Depression • Psychiatry

The synthetic opioid isotonitazene induces locomotor activity and reward effects through modulation of the central dopaminergic system in mice. (PubMed, Toxicol Appl Pharmacol) - "This effect was significantly suppressed by pretreatment with the opioid receptor antagonists naloxone (3 mg/kg) and β-FNA (1 mg/kg), the dopamine D1 receptor antagonist SCH23390 (0.5 mg/kg), and dopamine D2 receptor antagonist raclopride (6 mg/kg). These results suggest that isotonitazene, similar to fentanyl and morphine, is a compound with a high risk of forming drug dependence and reward effects via the dopaminergic nervous system. This study provides foundational data for biological evaluation of other nitazene compounds."

Journal • Preclinical • Addiction (Opioid and Alcohol) • DRD2