SCH-23390 / Boehringer Ingelheim - LARVOL DELTA

Role of the central adropin and its interaction with dopaminergic and serotoninergic system on feed intake in broiler chicken. (PubMed, Br Poult Sci) - "Co-injection of adropin and SCH23390 and for adropin and AMI-193 and for adropin and 5-HT2C receptor antagonist decreased hypophagia compared to the control group (p < 0.05).4. These results suggested that adropin has a hypophagic role and is linked to D1 and D2 and 5-HT2C receptors in neonatal broiler chickens."

Journal

Distinct Dopaminergic Modulation of Noise-Induced Plasticity With Divergent Effects of Dopamine Receptor Antagonism on Startle and Gap Inhibition (ARO 2026) - "Methods : Male Sprague Dawley rats (n=3-5/group) received bilateral IC cannula implantation and were assigned to saline control, D1 antagonist (R(+)-SCH-23390), or D2 antagonist (S(−)-Eticlopride) treatment groups...ABR amplitude preservation differed between receptor subtypes, with D2 receptor antagonism maintaining greater synchrony than D1 blockade... The preserved gap inhibition despite altered total startle suggests that IC dopaminergic circuits influence descending startle-generating pathways without disrupting ascending gap detection mechanisms. This dissociation indicates that calcium-dependent DA receptor signaling affects brainstem motor output circuits while sparing cortical auditory processing pathways essential for temporal gap detection. Future studies will examine how specific calcium channel manipulations in IC dopaminergic circuits differentially affect startle generation versus gap inhibition pathways, and whether targeting these distinct calcium..."

Immunology • Otorhinolaryngology

Caffeine potentiates the dependence induced by central nervous system depressants contained in over-the-counter medications in mice. (PubMed, J Toxicol Sci) - "The period required for dextromethorphan, diphenhydramine, bromovalerylurea, and morphine to acquire place preference was shortened by co-administration with caffeine, demonstrating that CNS stimulation enhances the preference of these sedatives in mice. Moreover, the preference for these drugs was suppressed by the dopamine D1 receptor antagonist SCH23390, and by the dopamine D2 receptor antagonist sulpiride, suggesting that dopamine is involved in the enhancing effect. These findings underscore the need to reconsider the active ingredients and distribution practices of OTC products, as the prolonged or inappropriate use of OTC medications and polypharmacy increases the risk of dependence."

Journal • Preclinical • CNS Disorders • Psychiatry • DRD2

Role of the dentate gyrus of hippocampus on acute pain modulation: Investigating of dopaminergic-opioidergic interactions in pain-related behaviors in the tail-flick test. (PubMed, Brain Res) - "Separate groups of animals received different doses of SCH23390 (6, 12, and 24 mmol/0.5 μL), a D1R antagonist, before injection of an effective dose of morphine (25 mmol/0.5 μL). The results suggest a strong interaction between opioidergic and dopaminergic systems in the DG in modulating acute pain. These findings can be used to reveal the precise mechanisms of pain modulation in brain circuits and to develop new strategies in pain management with greater efficacy and fewer side effects."

Journal • Pain

Neurobehavioral and Reinforcing Effects of Pregabalin in Mice. (PubMed, Behav Brain Res) - "Its ability to potentiate morphine's rewarding properties raises concern about abuse potential, particularly in opioid-exposed individuals. These findings highlight the need to consider sex as a biological variable when assessing the addictive risk of pregabalin."

Journal • Preclinical • Addiction (Opioid and Alcohol)

Increased Responsivity to Pharmacological Manipulations of Dopamine D1 Receptors in Binge Eating Prone Rats. (PubMed, Physiol Behav) - "Subsequently, rats received separate additional feeding tests following administration of either: the D1R agonist SKF 38393 (1.0, 3mg/kg); D1R antagonist SCH 23390 (0.1, 0.3 mg/kg); D2/3R agonist quinpirole (0.03, 0.1 mg/kg); or the D2R antagonist, raclopride (0,1, 0.2 mg/kg)...This general pattern of heightened responsivity to D1R manipulation was consistent with qPCR findings, which revealed in BEP compared to BER rats, a downregulation in the ventral tegmental area, and an upregulation in nucleus accumbens of D1R gene expression. Collectively these findings show that BEP rats overeat PF, which may be due to altered mesolimbic expression of D1R and corresponding heightened sensitivity to the rewarding properties of PF."

Journal • Preclinical • CNS Disorders

Mu-opioid and D1-like dopamine receptor crosstalk in dorsal CA1 hippocampus modulates inflammatory pain in rats. (PubMed, Behav Brain Res) - "In subsequent experiments, the D1R antagonist (SCH23390; 1.5, 3, 6, 12, or 24mmol/0.5μl) was microinjected into the dCA1 area of the hippocampus before injection of an effective dose of SKF38393 (12mmol/0.5μl) and morphine (10mmol/0.5μl). Results suggest that opioidergic and dopaminergic systems in the dCA1 interact to modulate pain relief. Cross-talk between D1Rs and MOR systems produces augmented analgesic effects, providing new insights for pain management research."

Journal • Preclinical • Pain

Neuromodulatory Regulation of Auditory Brainstem Responses: Neurochemical Interactions and Pharmacological Implications (ARO 2026) - "Auditory Brainstem Response (ABR) Recording ABRs were recorded under light anesthesia (e.g., ketamine/xylazine or isoflurane) to ensure minimal movement while preserving brainstem function...Pharmacological Manipulation To manipulate neuromodulatory activity, selective agonists and antagonists were administered systemically (intraperitoneally) or locally (via brainstem microinjection, if applicable) targeting specific neurotransmitter systems: Serotonergic: e.g., 5-HT1A agonist (8-OH-DPAT), antagonist (WAY-100635) Cholinergic: e.g., Nicotinic antagonist (mecamylamine), muscarinic agonist (oxotremorine) Dopaminergic: e.g., D1 receptor antagonist (SCH23390), D2 receptor agonist (quinpirole) Noradrenergic: e.g., α2 agonist (clonidine), β antagonist (propranolol) Histaminergic: e.g., H1 receptor antagonist (pyrilamine), H3 agonist (R-α-methylhistamine) Drugs were administered in isolation and in combination to assess potential interactive effects on ABR waveforms... This..."

Anesthesia

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