SCH-23390 / Boehringer Ingelheim - LARVOL DELTA

BASAL RELEASE OF 6-CYANODOPAMINE AND 6-NITRODOPAMINE FROM RAT ISOLATED AORTA AND THEIR ROLE IN VASCULAR RELAXATION. (PubMed, Eur J Pharmacol) - "Vascular reactivity was assessed in U-46619-precontracted rings with intact or removed endothelium and after pharmacological inhibition with Nω-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), indomethacin, SQ-22536, SCH-23390, and haloperidol...SQ-22536 also attenuated forskolin- and iloprost-induced relaxation, supporting involvement of adenylyl cyclase/cAMP signaling in 6-CYD responses...Rat thoracic aorta basally releases 6-CYD and 6-ND, and although both act as potent vasodilators, they have distinct mechanisms of action. These findings shed new light on mechanisms by which the vascular endothelium regulates vascular tone."

Journal • Preclinical • Cardiovascular • Hypertension

Acute Pharmacological Assessment of Dopaminergic and Glutamatergic Involvement in Nitric Oxide-Associated Feed Intake in Male Neonatal Broilers. (PubMed, Physiol Behav) - "Chicks received intracerebroventricular (ICV) administration of L‑arginine (NO precursor), L‑NAME (NOS inhibitor), MK‑801 (NMDA antagonist), MSPG (metabotropic glutamate antagonist), SCH23390 (D1 antagonist) and AMI‑193 (D2 antagonist), alone or in combination...NMDA and D1 receptor signaling may contribute to L‑arginine‑induced hypophagia, whereas L-NAME-induced hypophagia was enhanced by NMDA receptor blockade but was not significantly modified by metabotropic glutamate, D1, or D2 receptor blockade under the present conditions. However, the present acute ICV pharmacological approach does not establish the underlying physiological or cellular mechanisms, which require direct neurochemical and molecular investigation."

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Pharmacological activation of dopamine receptor D1 attenuates TGF-β-induced epithelial-mesenchymal transition in A549 and BEAS-2B cells. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Dopamine analogues, DRD1 agonists, and the DRD1 antagonist SCH23390 were used to evaluate the role of DRD1...In these pulmonary epithelial cell-line models, DRD1 agonist treatment attenuated TGF-β-induced EMT-related changes and was associated with restoration of cAMP/PKA signaling. These in vitro findings identify DRD1 signaling as a candidate mechanism for further preclinical study; confirmation in primary cells, epithelial-fibroblast systems, and animal models is required before therapeutic relevance to pulmonary fibrosis can be inferred."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CDH1 • SNAI1 • TGFB1 • VIM • ZEB1

Moringa oleifera Lam. Seed Lectin (WSMoL) Attenuates Parkinsonian Symptoms in Mice via Anti-Inflammatory, Antioxidant, and Neurotransmitter-Modulating Effects. (PubMed, Chem Biodivers) - "To assess dopaminergic involvement, another group received the D1 receptor antagonist SCH-23390 co-administered with WSMoL (4 mg/kg)...The data show that D1 receptor-mediated signaling contributes to WSMoL effects. In conclusion, WSMoL attenuates motor deficits and neuroinflammation in a PD model, which supports its potential as a neuroprotective agent and warrants further mechanistic and translational studies."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CAT • IFNG • IL17A • IL6 • TNFA

Dissociable roles of dopamine D1 and nicotinic receptors in nicotine-motivated responding and impulsive action in a Go/No-Go self-administration task. (PubMed, bioRxiv) - "The D1 receptor antagonist SCH23390 reduced nicotine intake and active lever responding during Go periods and affected the percentage of active lever responses during No-Go periods...These findings suggest that nicotinic acetylcholine receptor signaling plays a major role in nicotine-induced impulsive action, whereas D1 receptor signaling contributes more clearly to nicotine-motivated responding. D1 receptor agonism may reduce nicotine-motivated behavior without affecting nicotine-induced impulsive action."

Journal • Nicotine Addiction

Bioamine disruption leads to memory deficits in the whip spider, Phrynus marginemaculatus. (PubMed, J Comp Physiol A Neuroethol Sens Neural Behav Phys) - "Subjects were trained on an olfactory memory paradigm, subsequently injected with physiological saline, the serotonin receptor antagonist methiothepin mesylate (MET), or the dopamine receptor antagonist SCH-23390 (SCH), and tested for memory retention 24 h afterwards...Additionally, there were no significant differences in locomotor activity between treatment and control groups on test day (p > 0.05). Together, these results are consistent with serotonergic and dopaminergic signaling contributing to olfactory memory consolidation without grossly impairing locomotion in Phrynus marginemaculatus."

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Increased activity of DRD1-MSNs in dorsolateral striatum underlies Cry1Δ11 mutation-induced repetitive behaviors. (PubMed, Transl Psychiatry) - "Critically, systemic administration of the DRD1 antagonist SCH23390 fully rescued both neuronal hyperactivity and behavioral abnormalities in mutant mice. Together, our findings establish a direct mechanistic link among a core circadian gene mutation, striatal dopaminergic hyperactivity, and repetitive behaviors, thereby identifying aberrant DRD1 signaling in the dorsolateral striatum as a promising target for therapeutic intervention."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • CRY1 • DRD1

ACUTE PHYSICAL EXERCISE ENHANCES MEMORY PERSISTENCE IN FEMALE RATS VIA HIPPOCAMPAL CATECHOLAMINERGIC RECEPTORS. (PubMed, Physiol Behav) - "Adult female Wistar rats were trained in the novel object recognition (NOR) task and, immediately afterward, were subjected to acute PE (30 min at 60-70% of VO₂max), followed by intrahippocampal infusions of vehicle (VEH), the D1/D5 dopamine receptor antagonist SCH23390, or the β-adrenergic receptor antagonist timolol. In this context, acute PE appears to facilitate memory persistence in females through hippocampal catecholaminergic mechanisms, highlighting an important role for dopamine and norepinephrine signaling in exercise-induced cognitive modulation. Moreover, the results suggest a possible temporal dependence of catecholaminergic involvement in female memory processing, with these pathways being required early during consolidation for proper memory stabilization."

Journal • Preclinical

VTA dopamine inputs activate accumbal D1 receptors to promote alcohol seeking. (PubMed, iScience) - "Systemic D1R antagonist SCH23390 suppresses cue-induced seeking and reverses c-Fos activation in the NAc and ventral pallidum. Chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons attenuates craving, an effect fully rescued by intra-NAc D1R agonist SKF38393 without affecting locomotion. These findings establish that dopaminergic projections from the VTA to the NAc drive cue-specific alcohol seeking through D1 receptor-dependent manner."

Journal • Addiction (Opioid and Alcohol) • FOS

Association of central α-klotho with dopaminergic and melanocortin receptors on feed intake regulation in chicken. (PubMed, Poult Sci) - "In experiment 1, the group (A) received injections of saline, group (B) SCH23390 (D1 receptor antagonist, 5 nmol), group (C) α-klotho (4 µg) and group (D) co-injection of the SCH23390 + α-klotho...Co-injection of the selective MC4 receptor antagonist decreased α-klotho-induced hypophagic effect compared to control group (P < 0.05). Findings suggested α-klotho-induced hypophagia mediates by D1 and D2 dopaminergic as well as MC3 and MC4 melanocortin receptors in neonatal broiler chicken."

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Effect of aripiprazole on cytokine production by T cells in schizophrenia (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "Aripiprazole may exert anti-inflammatory effects in schizophrenia by inhibiting the secretion of pro-inflammatory cytokines by T cells. This effect is likely mediated through D2DR activation."

Journal • CNS Disorders • Psychiatry • Schizophrenia • DRD2 • IFNG • IL17A

Reproductive experience modifies the dopaminergic system of postpartum estrous rats: changes in the sensitivity to the behavioural effects of sch-23390 and in its receptors' binding. (PubMed, Psychopharmacology (Berl)) - No abstract available

Journal • Preclinical

Unpredictable Chronic Mild Stress Upregulates Dopamine Receptor Expression Independent of Fatty Acid-Binding Protein 7 Gene Deletion. (PubMed, Neurochem Res) - "After the stress paradigm, D1R and D2R levels were measured with in vitro autoradiography using [3H] SCH23390 and [3H] Spiperone, respectively...The UCMS paradigm upregulates D1R and D2R binding independent of FABP7 gene deletion, suggesting a compensatory role of other FABPs in the brain in maintaining dopaminergic homeostasis. This stress-induced shift in D1R: D2R ratio may underlie the pathogenesis of major depressive disorder and substance use disorder, as well as the high comorbidity among these conditions."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • DRD2 • FABP7

Dopamine-induced vasoconstriction is attenuated by endothelial nitric oxide in isolated rat aorta. (PubMed, Eur J Pharmacol) - "Effects of the nitric oxide synthase inhibitor Nw-ntiro-L-arginine methyl ester (L-NAME), non-specific guanylate cyclase (GC) inhibitor methylene blue, nitric oxide-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), calmodulin inhibitor calmidazolium, SCH-23390, sulpiride, haloperidol, and prazosin on dopamine-induced contraction in endothelium-intact aortas were examined. Dopamine also increased eNOS phosphorylation and calcium levels in HUVECs, whereas haloperidol or prazosin inhibited these responses. These findings suggest that dopamine-induced vasoconstriction is attenuated by a pathway involving calmodulin-eNOS-GC-cGMP in endothelium-intact rat aortas, mediated by alpha-1 adrenoceptors."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease • NOS3

Involvement of D1- and D2-like dopamine receptors in the hippocampal CA1 region in mediating the restraint stress-induced analgesia in the rats. (PubMed, IBRO Neurosci Rep) - "This study's findings indicated that the administration of SCH23390 and sulpiride into the CA1 area of the hippocampus at the maximal doses (4 µg/0.5 µl; P < 0.001) markedly diminished the analgesic benefits of RS in the acute pain paradigm. The magnitude of estimated ED50s in the effect of these antagonists on reducing the RS-induced analgesia was 1.64 µg for SCH23390 and 2.79 µg for sulpiride, suggesting that both dopamine D1-like and D2-like receptors in the CA1 region of the hippocampus likely contribute to the analgesic effects of RS in the rats."

Journal • Preclinical • Pain

Possible Role of Dopamine in the Enhancement of Intrahippocampal Arc Protein Expression Induced by Post-Learning Noradrenergic Stimulation of the Basolateral Amygdala. (PubMed, Int J Mol Sci) - "Novelty-induced dopamine release in the dHipp was enhanced by omitting habituation prior to training, and the contribution of dopamine signaling was further evaluated using pre-infusion administration of the D1/D5 receptor antagonist SCH 23390...This interaction is considered essential for the initial stages of memory consolidation. The obtained results indicate the presence of a region-specific interaction between BLA modulatory inputs and intrahippocampal dopaminergic transmission, the mechanisms of which remain to be elucidated."

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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."

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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."

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