OBJECTIVE: To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome. METHODS: From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded. RESULTS: Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment. CONCLUSIONS The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589).
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Rhinitis, Allergic/drug therapy* ; Female ; Adult ; Double-Blind Method ; Quality of Life ; Qi ; Middle Aged ; Loratadine/therapeutic use* ; Medicine, Chinese Traditional ; Syndrome ; Lung/drug effects* ; Young Adult ; Treatment Outcome

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

To analyze the efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine as well as desloratadine alone in the treatment of chronic urticaria by Meta-analysis,in order to provide evidence-based reference for clinical treatment.PubMed,CBM,Wan Fang,VIP database and CNKI database were retrieved to collect randomized controlled trials( RCT) about Tripterygium Glycosides Tablets combined with desloratadine( test group) as well as desloratadine alone( control group) in the treatment of chronic urticaria. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation( a total of 15 RCTs were included,involving 1 411 patients). Meta-analysis showed that the total effective rate( RR = 1. 28,95%CI[1. 22,1. 35],P<0. 000 01) and the quality of life improvement rate( RR = 1. 49,95% CI[1. 33,1. 66],P< 0. 000 01) of the test group were better than those of the control group,and the recurrence rate( RR = 0. 29,95%CI[0. 21,0. 40],P<0. 000 01) was significantly lower than that of the control group,with statistically significant differences; there was no statistically significant difference in the incidence of adverse reactions( RR = 1. 02,95%CI[0. 68,1. 53],P = 0. 92) compared with the control group. Based on the included RCTs,the efficacy of Tripterygium Glycosides Tablets combined with desloratadine in the treatment of chronic urticaria were superior to those of desloratadine alone,with similarity in safety. However,due to the low quality of RCTs and the lack of large-scale multi-center studies,the results shall not be further verified by clinical trials.
Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Glycosides ; therapeutic use ; Humans ; Loratadine ; analogs & derivatives ; therapeutic use ; Quality of Life ; Randomized Controlled Trials as Topic ; Tablets ; Tripterygium ; chemistry ; Urticaria ; drug therapy

Despite some innate limitations, animal models are a potent investigative tool when used to model specific symptoms of a disorder. For example, MK-801, an N-methyl-D-aspartate receptor antagonist, is used as a pharmacological tool to induce symptoms found in some neuropsychiatric disorders. However, a close examination of literature suggests that the application window of MK-801 doses is relatively narrow between individual behavioral paradigms, necessitating careful characterization of the evoked behavioral aberrations and the doses used to induce them. Moreover, variation in behaviors depending on the animal strain, gender of the subject, and the timing of administration is observed, making it difficult to compare the behavioral characteristics reported in different studies. We aim to characterize the behavioral aberrations induced by different doses of MK-801 in CD-1 mice and create a ready reference for future studies. We used CD-1 mice to recapitulate behavioral impairments resulting from acute administration of MK-801. In 0.1 mg kg⁻¹, we observed diminished spontaneous alteration during the Y-maze test, while 0.12 mg kg⁻¹ resulted in hyperlocomotion and social deficit. Mice treated with 0.2 and 0.3 mg kg⁻¹ of MK-801 demonstrated a decreased self-grooming. Finally, all doses significantly impaired cliff avoidance behaviors suggesting increased impulsivity. These results affirm that MK-801 can effectively model various symptoms of different neuropsychiatric disorders in a dose-dependent manner. The observed sensitivity against spatial-memory impairment and impulsive behaviors at low concentration of MK-801 suggest that MK801 may modulate cognitive function and impulsivity in even lower concentration before it can modulate other behavioral domains.
Animals ; Avoidance Learning ; Cognition ; Dizocilpine Maleate ; Impulsive Behavior ; Mice ; Models, Animal ; N-Methylaspartate

BACKGROUND: The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. METHODS: Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. RESULTS: Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. CONCLUSIONS: The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.
Adenosine ; Amitriptyline ; Animals ; Antidepressive Agents, Tricyclic ; Cyclic AMP Response Element-Binding Protein ; Cytokines ; Humans ; Hyperalgesia ; Immunoblotting ; Ligation ; Male ; Neuralgia ; Phosphotransferases ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P1 ; Spinal Nerves

Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BP-induced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
Animals ; Brain ; drug effects ; metabolism ; pathology ; Cognitive Dysfunction ; drug therapy ; metabolism ; pathology ; Disease Models, Animal ; Dizocilpine Maleate ; pharmacology ; Excitatory Amino Acid Antagonists ; pharmacology ; Hydrocarbons, Brominated ; Inflammasomes ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; physiology ; Microglia ; drug effects ; metabolism ; pathology ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Neurons ; drug effects ; metabolism ; pathology ; Nootropic Agents ; pharmacology ; Random Allocation ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; metabolism ; Spatial Memory ; drug effects ; physiology ; Specific Pathogen-Free Organisms

PURPOSE: Headache is a common symptom during childhood. It is usually persistent and requires special care. This study aimed to identify the characteristics of headache in children < 7 years of age. METHODS: We reviewed 3 years of clinical files on children < 7 years of age with a chief complaint of headache. RESULTS: This study included 146 children (66 males, 80 females; mean age, 5.5±1.0 years). Mean symptom duration was 5.8±7.9 months. Attack durations were longer than 2 hours in 31 patients, shorter than 2 hours in 70 patients, and unchecked in 45 patients. Attack frequency was 15.1±10.6 times per month. Pain locations and characteristics were also variable. Mean pain severity score was 5.1±2.2 on the visual analog scale. Of 38 patients who underwent electroencephalography, 9 showed positive findings. Of 41 who underwent brain magnetic resonance imaging, 20 showed positive findings. The diagnoses were migraine (including probable migraine) in 34, tension-type headache in 5, and congenital malformations in 3. Medications were used in 29 patients: acetaminophen in 17, ibuprofen in 8, naproxen sodium in 1, and topiramate or amitriptyline in 3. CONCLUSION: In children aged < 7 years, headache has a relatively benign course, but detailed history taking is needed for more accurate diagnosis.
Acetaminophen ; Amitriptyline ; Brain ; Child* ; Diagnosis ; Electroencephalography ; Female ; Headache* ; Humans ; Ibuprofen ; Magnetic Resonance Imaging ; Male ; Migraine Disorders ; Naproxen ; Tension-Type Headache ; Visual Analog Scale

Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 (5-HT₃) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with 5-HT₃ receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the 5-HT₃ receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express 5-HT₃ receptors. To elucidate the mechanism of amitriptyline, we simulated the 5-HT₃ receptor currents using Berkeley Madonna® software and calculated the rate constants of the agonist binding and receptor transition steps. The 5-HT₃ receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the 5-HT₃ receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the 5-HT₃ receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a 5-HT₃ receptor, a potential target of neurologic and psychiatric diseases through this study.
Amitriptyline* ; Constriction ; Depression ; Methods ; Neuralgia ; Neuroblastoma ; Serotonin*

BACKGROUND: Use of antidepressant medications has been linked to detrimental impacts on bone mineral density and osteoporosis; however, the cellular basis behind these observations remains poorly understood. The effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. In this study, we hypothesized that antidepressants have a class- and dose-dependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism. METHODS: Human MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media was added, supplemented with five increasing concentrations of amitriptyline (0.001–10 µM), venlafaxine (0.01–25 µM), or fluoxetine (0.001–10 µM). Alizarin red staining (mineralization), alkaline phosphatase (osteoblastogenesis), and oil red O (adipogenesis) assays were performed at timed intervals. In addition, cell viability was assessed using a MTT. RESULTS: We found that fluoxetine had a significant inhibitory effect on mineralization. Furthermore, adipogenic differentiation of hMSC was affected by the addition of amitriptyline, venlafaxine, and fluoxetine to the media. Finally, none of the tested medications significantly affected cell survival. CONCLUSIONS: This study showed a divergent effect of three antidepressants on hMSC differentiation, which appears to be independent of class and dose. As fluoxetine and amitriptyline, but not venlafaxine, affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.
Adipogenesis ; Alkaline Phosphatase ; Amitriptyline ; Antidepressive Agents ; Bone Density ; Cell Survival ; Fluoxetine ; Humans ; Mesenchymal Stromal Cells ; Metabolism ; Miners ; Osteoblasts ; Osteoporosis ; Serotonin Plasma Membrane Transport Proteins ; Venlafaxine Hydrochloride

OBJECTIVE: The primary aim of this study was to further characterize the acute effects of amitriptyline (AMI) and escitalopram (ESC) on serum levels of ghrelin, leptin, cortisol and prolactin in healthy humans. METHODS: Eleven healthy male participants received a single dose of AMI 75 mg, ESC 10 mg, or placebo (PLA) at 9:00 PM in a double blind, randomized, controlled, repeated measures study separated by one week. Fasting morning serum levels (7:00 AM) of ghrelin, leptin, cortisol and prolactin were assessed. RESULTS: A repeated measures multivariate analysis of variance revealed a significant main effect for the factor condition (AMI, ESC, PLA). Subsequent univariate analyses demonstrated significant condition effects for ghrelin and cortisol. Post-hoc analyses demonstrated a significant reduction of ghrelin levels after AMI in comparison to PLA, and a significant reduction of cortisol levels after AMI in comparison to both ESC and PLA. Other contrasts did not reach statistical significance. CONCLUSION: Administration of a single dose of AMI, but not of ESC, leads to a significant reduction in morning serum ghrelin and cortisol levels. No effects on leptin and prolactin levels were observed. The differential impact of AMI and ESC on hormones might contribute to different adverse effect profiles of both substances.
Amitriptyline* ; Citalopram* ; Fasting ; Ghrelin ; Healthy Volunteers* ; Humans ; Hydrocortisone ; Leptin ; Male ; Multivariate Analysis ; Prolactin ; Weight Gain