Effect Of Cyproheptadine Research Articles

Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial.

Serotonin is a mediator of pulmonary hypoxic vasoconstriction. Experimental studies have shown that serotonin-mediated pulmonary vasoconstriction can be inhibited by cyproheptadine. The aim of this study is to assess whether treatment with cyproheptadine compared to usual care increases ventilatory support-free days during the first 28 days in patients with coronavirus disease 2019 (COVID-19) requiring ventilatory support. This randomized, single-center, open-label clinical trial included patients who were admitted to the intensive care unit (ICU) requiring ventilatory support due to COVID-19. Patients allocated to the intervention group received cyproheptadine for 10 days. The primary outcome was ventilator-free days during the first 28 days. Nineteen patients were randomized to receive cyproheptadine and 21 to the control group. The number of ventilatory support-free days during the first 28 days was not different between the two groups (15.0; 95% CI, 0.0-24.0 days in the control group vs 7.0; 95% CI, 0.0-19.0 days in the intervention group; p = 0.284). In patients with COVID-19 and in need of ventilatory support, the use of cyproheptadine plus usual care, compared with usual care alone, did not increase the number of ventilatory support-free days in 28 days. Boniatti MM, Nedel WL, Rihl MF, Schwarz P, Parolo E, Moretti MMS, et al. Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial. Indian J Crit Care Med 2023;27(7):517-521.

Abstract 4166: Effects of cyproheptadine in eliciting natural killer cell-mediated immune response in bladder cancer

Abstract Bladder cancer is one of the most common occurring cancers in urothelial carcinoma. The previous study suggested that cancer cells undergo immunoevasion due to epigenetic silencing of NKG2DL, in which NKG2D-NKG2DL interaction induced natural killer (NK) cell-mediated cytotoxicity. We hypothesized that NK-mediated cytotoxicity can be reactivated by restoring the expression of NKG2DL on tumor cells. Our previous studies demonstrated that cyproheptadine (CPH) is a novel HDAC inhibitor exhibiting antitumor activity by cell cycle arrest and apoptosis. To understand the mechanism behind, RNA-seq showed an upregulation of ULBP2, a NKG2DL, in bladder cancer cells treated with CPH. Interestingly, upregulation of ULBP2, was accompanied with the enrichment of H3K27Ac and H3K4me3 at ULBP2 promoter, was observed in cells treated with CPH. Increased NK-specific lysis was observed in CPH-treated cells co-cultured with NK-92 cells. More importantly, treatment of CPH enhanced the efficacy of immune checkpoint inhibitor in a syngeneic mice bladder cancer model. In conclusion, our results suggested that CPH may be a novel HDAC inhibitor which may elicit immune response in NK-cell dependent manner. Citation Format: Himani Kumari, Guan-Ling Lin, Chih-Chieh Yeh, Ciao-Ni Chen, Yu-Ming Chuang, Wan-Hong Huang, Wen-Long Huang, Steven Lin, Michael W. Chan. Effects of cyproheptadine in eliciting natural killer cell-mediated immune response in bladder cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4166.

Blockade of 5-HT2 receptors suppresses rate of torque development and motor unit discharge rate during rapid contractions.

Serotonin (5-HT) is a neuromodulator that is critical for regulating the excitability of spinal motoneurons and the generation of muscle torque. However, the role of 5-HT in modulating human motor unit activity during rapid contractions has yet to be assessed. Nine healthy participants (23.7 ± 2.2 yr) ingested 8 mg of the competitive 5-HT2 antagonist cyproheptadine in a double-blinded, placebo-controlled, repeated-measures experiment. Rapid dorsiflexion contractions were performed at 30%, 50%, and 70% of maximal voluntary contraction (MVC), where motor unit activity was assessed by high-density surface electromyographic decomposition. A second protocol was performed where a sustained, fatigue-inducing dorsiflexion contraction was completed before undertaking the same 30%, 50%, and 70% MVC rapid contractions and motor unit analysis. Motor unit discharge rate (P < 0.001) and rate of torque development (RTD; P = 0.019) for the unfatigued muscle were both significantly lower for the cyproheptadine condition. Following the fatigue inducing contraction, cyproheptadine reduced motor unit discharge rate (P < 0.001) and RTD (P = 0.024), whereas the effects of cyproheptadine on motor unit discharge rate and RTD increased with increasing contraction intensity. Overall, these results support the viewpoint that serotonergic effects in the central nervous system occur fast enough to regulate motor unit discharge rate during rapid powerful contractions.NEW & NOTEWORTHY We have shown that serotonin activity in the central nervous system plays a role in regulating human motor unit discharge rate during rapid contractions. Our findings support the viewpoint that serotonergic effects in the central nervous system are fast and are most prominent during contractions that are characterized by high motor unit discharge rates and large amounts of torque development.

Effects of cyproheptadine on body weight gain in children with nonorganic failure to thrive in Taiwan: A hospital-based retrospective study.

Failure to thrive (FTT) impairs the expected normal physical growth of children. This study aimed to evaluate the effects of cyproheptadine hydrochloride on growth parameters in prepubertal children with FTT. The medical records of prepubertal children who were newly diagnosed with FTT at China Medical University Hospital between 2007 and 2016 were retrospectively examined. The patients were divided into two groups depending on whether they had (T-group) or had not (NT-group) received cyproheptadine hydrochloride (0.3 mg/kg daily) for at least 14 days. The mean length of the treatment period was 97.22 days (range: 14-532 days). Weight, height, and body mass index were adjusted for age using the median values in the growth charts for Taiwanese boys and girls as the reference. A total of 788 patients aged 3-11 years were enrolled, 50 in the T-group and 738 in the NT-group. No statistically significant difference in the median age-adjusted weight value was noted between the T-group and NT-group during the follow up period. In the T-group, age-adjusted weight and body mass index were inversely associated with age (P <0.001, P <0.001) and positively associated with medication duration (P = 0.026, P = 0.04). Our findings underscore the positive association between cyproheptadine hydrochloride treatment and weight gain among prepubertal children. Further prospective clinical studies with a. longer and consistent treatment course is warranted.

Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study

PurposeCyproheptadine, an antihistamine and antiserotonergic agent, is an appetite stimulant that is efficacious in promoting weight gain in children and adults with poor appetite. Despite numerous studies showing that cyproheptadine achieved positive outcomes, studies documenting its effectiveness on appetite are limited. This study evaluated the efficacy and tolerability of cyproheptadine in adults with poor appetite in South Korea. MethodsPatients aged 19 to 64 years with poor appetite were randomly assigned to receive either cyproheptadine or placebo for 8 weeks. The primary end point was the difference between the groups in change in appetite, as measured by the Korean version of the Edmonton Symptom Assessment System from the beginning to the end of the study period. The secondary end points included effects on weight, anthropometrics, body composition, Simplified Nutritional Appetite Questionnaire–measured appetite, and toxicities. A total of 375 patients were randomly assigned to the two groups (189 cyproheptadine, 186 placebo). FindingsThe cyproheptadine group experienced a mean (SD) change in appetite score of –2.42 (0.12) compared with –2.03 (0.13) in the placebo arm, representing a statistically significant appetite gain in the cyproheptadine group (difference, +0.38 [0.18]; 95% CI, –0.73 to –0.04; P = 0.0307). Patients in the cyproheptadine group experienced significant increases in weight and body mass index. The most common adverse event was somnolence, as predicted. Cyproheptadine was well tolerated, with one serious adverse event (colitis) which was classified as a moderate adverse effect unlikely to be related to the study drug. ImplicationsWe present the largest randomized, double-blind, placebo-controlled clinical trial of cyproheptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cyproheptadine. Cyproheptadine is a safe treatment option in patients with poor appetite. Our findings provide important information for the use of cyproheptadine to ameliorate poor appetite in adults. Further randomized studies focused on the effect of cyproheptadine in older populations are needed.

Preventive effect of cyproheptadine on sleep and appetite disorders induced by methylphenidate: an exploratory randomised, double-blinded, placebo-controlled clinical trial

Objectives: Insomnia and loss of appetite are the most common side effects of methylphenidate in patients with attention deficit/hyperactivity disorder (ADHD). The adverse effects may limit optimal dosing and patients’ compliance with treatment leading to the discontinuation of treatment. This research evaluates the preventive effects of cyproheptadine on sleeping and appetite disorders induced by methylphenidate in ADHD children.Methods: During this exploratory, randomised, double-blinded, placebo-controlled clinical trial, forty patients with ADHD diagnosis who had received methylphenidate randomly were assigned to participate in the cyproheptadine or the placebo group. Patients’ weight and Pittsburgh Sleep Quality Index (PSQI) score were recorded at baseline, after four, six and eight weeks of treatment. The ADHD Parent Rating Scale-V score was also defined at the beginning and the end of study for each patient.Results: There was no significant difference between the cyproheptadine and the placebo groups regarding their weight, rate of growth and PSQI score in the monthly assessment. In addition, there was no significant difference in response to the therapy between the two groups.Conclusions: Based on our findings, cyproheptadine does not have any considerable preventive effect on sleeping and appetite disorders induced by methylphenidate in ADHD children.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT2015070623099N1.

Effect of Cyproheptadine on Weight and Growth Velocity in Children With Silver-Russell Syndrome.

Nutritional management of children with Silver-Russell syndrome (SRS) is crucial, especially before initiating growth hormone therapy. Since cyproheptadine (CYP) has been reported to be orexigenic, we retrospectively investigated the effects of CYP on changes in weight and height in patients with SRS. Anthropometric parameters (weight [W], length or height [H], weight on expected weight for height [W/H], and body mass index) were recorded for 34 children with SRS receiving CYP. We specifically analyzed the anthropometric parameters (expressed in median) in a group of 23 patients treated with CYP at baseline (M0-CYP) and every 3 months (M3 to M12-CYP) after the initiation of CYP treatment. The 23 children with SRS treated by CYP only had weight stagnation during the months preceding the start of treatment. Anthropometric parameters, especially the weight, differed significantly between M0-CYP and all other times (M3, M6, M9, M12-CYP). After 1 year of treatment, a gain in overall length/height and weight was observed (W: +1.1 standard deviations from the mean [SDS]; H: +0.5 SDS). At M3, significant improvements in W/H (74.9% vs 79.3% [P = 0.01]) and body mass index (-3.4 vs -2.4 SDS [P = 0.001]) were also observed. Twenty-one patients (91%) improved their weight by at least +0.5 SDS, and 12 (52%) by at least +1 SDS. Our results show that CYP can be effective in patients with SRS with significant improvements in growth velocity and nutritional status before initiation of growth hormone therapy. Further prospective studies are required to confirm these results.

Cyproheptadine, an antihistaminic drug, inhibits proliferation of hepatocellular carcinoma cells by blocking cell cycle progression through the activation of P38 MAP kinase.

BackgroundHepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide. However, current chemotherapeutic drugs for HCC are either poorly effective or expensive, and treatment with these drugs has not led to satisfactory outcomes. In a 2012 case report, we described our breakthrough finding in two advanced HCC patients, of whom one achieved complete remission of liver tumors and the other a normalized α-fetoprotein level, along with complete remission of their lung metastases, after the concomitant use of thalidomide and cyproheptadine. We assumed the key factor in our effective therapy to be cyproheptadine. In this study, we investigated the antiproliferative effects and molecular mechanisms of cyproheptadine.MethodsThe effect of cyproheptadine on cell proliferation was examined in human HCC cell lines HepG2 and Huh-7. Cell viability was assayed with Cell Counting Kit-8; cell cycle distribution was analyzed by flow cytometry. Mechanisms underlying cyproheptadine-induced cell cycle arrest were probed by western blot analysis.ResultsCyproheptadine had a potent inhibitory effect on the proliferation of HepG2 and Huh-7 cells but minimal toxicity in normal hepatocytes. Cyproheptadine induced cell cycle arrest in HepG2 cells in the G1 phase and in Huh-7 cells at the G1/S transition. The cyproheptadine-induced G1 arrest in HepG2 cells was associated with an increased expression of HBP1 and p16, whereas the G1/S arrest in Huh-7 cells was associated with an increase in p21 and p27 expression and a dramatic decrease in the phosphorylation of the retinoblastoma protein. Additionally, cyproheptadine elevated the percentage of Huh-7 cells in the sub-G1 population, increased annexin V staining for cell death, and raised the levels of PARP and its cleaved form, indicating induction of apoptosis. Finally, cyproheptadine-mediated cell cycle arrest was dependent upon the activation of p38 MAP kinase in HepG2 cells and the activation of both p38 MAP kinase and CHK2 in Huh-7 cells.ConclusionsOur results demonstrate that a non-classical p38 MAP kinase function, regulation of cell cycle checkpoints, is one of the underlying mechanisms promoted by cyproheptadine to suppress the proliferation of HCC cells. These results provide evidence for the drug’s potential as a treatment option for liver cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1137-9) contains supplementary material, which is available to authorized users.

Cyproheptadine Enhances the IK of Mouse Cortical Neurons through Sigma-1 Receptor-Mediated Intracellular Signal Pathway

Cyproheptadine (CPH) is a histamine- and serotonin-receptor antagonist, and its effects are observed recently in the modulation of multiple intracellular signals. In this study, we used cortical neurons and HEK-293 cells transfected with Kv2.1 α-subunit to address whether CPH modify neural voltage-gated K+ channels by a mechanism independent of its serotonergic and histaminergic properties. Our results demonstrate that intracellularly delivered CPH increased the I K by reducing the activity of protein kinas A (PKA). Inhibition of Gi eliminated the CPH-induced effect on both the I K and PKA. Blocking of 5-HT-, M-, D2-, H1- or H2- type GPCR receptors with relevant antagonists did not eliminate the CPH-induced effect on the I K. Antagonists of the sigma-1 receptor, however, blocked the effect of CPH. Moreover, the inhibition of sigma-1 by siRNA knockdown significantly reduced the CPH-induced effect on the I K. On the contrary, sigma-1 receptor agonist mimicked the effects of CPH on the induction of I K. A ligand-receptor binding assay indicated that CPH bound to the sigma-1 receptor. Similar effect of CPH were obtained from HEK-293 cells transfected with the α-subunit of Kv2.1. In overall, we reveal for the first time that CPH enhances the I K by modulating activity of PKA, and that the associated activation of the sigma-1 receptor/Gi-protein pathway might be involved. Our findings illustrate an uncharacterized effect of CPH on neuron excitability through the I K, which is independent of histamine H1 and serotonin receptors.

A clozapine-like effect of cyproheptadine on progressive ratio schedule performance

The atypical antipsychotic drug clozapine has multiple pharmacological actions, some of which, including 5-hydroxytryptamine (5-HT₂) and histamine (H₁) receptor antagonist effects, are shared by the non-selective 5-HT receptor antagonist cyproheptadine. Atypical antipsychotics have a characteristic profile of action on operant behaviour maintained by progressive ratio schedules, as revealed by Killeen's (1994) mathematical model of schedule controlled behaviour. These drugs increase the values of a parameter that expresses the 'incentive value' of the reinforcer (a) and a parameter that is inversely related to the 'motor capacity' of the organism (δ). This experiment examined the effects of acute treatment with cyproheptadine and clozapine on performance on a progressive ratio schedule of food reinforcement in rats; the effects of a conventional antipsychotic, haloperidol, and two drugs with food intake-enhancing effects, chlordiazepoxide and Δ⁹-tetrahydrocannabinol (THC), were also examined. Cyproheptadine (1, 5 mg kg⁻¹) and clozapine (3.75, 7.5 mg kg⁻¹) increased a and δ. Haloperidol (0.05, 0.1 mg kg⁻¹) reduced a and increased δ. Chlordiazepoxide (3, 10 mg kg⁻¹) increased a but reduced δ. THC (1, 3 mg kg⁻¹) had no effect. Interpretation based on Killeen's (1994) model suggests that cyproheptadine and clozapine enhanced the incentive value of the reinforcer and impaired motor performance. Motor impairment may be due to sedation (possibly reflecting H₁ receptor blockade). Enhancement of incentive value may reflect simultaneous blockade of H₁ and 5-HT₂ receptors, which has been proposed as the mechanism underlying the food intake-enhancing effect of cyproheptadine. In agreement with previous findings, haloperidol impaired motor performance and reduced the incentive value of the reinforcer. Chlordiazepoxide's effect on a is consistent with its food intake-enhancing effect.

Effects of cyproheptadine and cetirizine on eosinophilic airway inflammation in cats with experimentally induced asthma

To determine whether oral administration of cyproheptadine or cetirizine blocks the action of serotonin and histamine, respectively, and results in diminished eosinophilic airway inflammation in cats with experimentally induced asthma. 9 cats in which asthma was experimentally induced through exposure to Bermuda grass allergen (BGA) during a 3-month period. Cats were randomized to receive monotherapy with each of 3 treatments for 1 week: placebo (flour in a gelatin capsule, PO, q 12 h), cyproheptadine (8 mg, PO, q 12 h), or cetirizine (5 mg, PO, q 12 h). A 1-week washout period was allowed to elapse between treatments. Prior to and following each 1-week treatment period, blood and bronchoalveolar lavage fluid (BALF) samples were collected. The percentage of eosinophils in BALF was evaluated to determine treatment efficacy. Serum and BALF BGA-specific immunoglobulin contents and plasma and BALF histamine concentrations were determined via ELISAs. Plasma and BALF serotonin concentrations were measured by use of a fluorometric method. The mean +/- SD percentage of eosinophils in BALF did not differ significantly among treatment groups (placebo, 40 +/- 22%; cyproheptadine, 27 +/- 16%; and cetirizine, 31 +/- 20%). Among the treatment groups, BGA-specific immunoglobulin content and histamine and serotonin concentrations were not significantly different. In cats with experimentally induced asthma, cyproheptadine and cetirizine were not effective in decreasing airway eosinophilic inflammation or in altering several other measured immunologic variables. Neither cyproheptadine nor cetirizine can be advocated as monotherapy for cats with allergen-induced asthma.

Interactive effect of histamine and prostaglandin D 2 on nasal allergic symptoms in rats

This study was undertaken to investigate the interactive effect of histamine and prostaglandin D 2 in nasal allergic symptoms in rats. The intranasal application of histamine at doses lower than 10 μmol/site caused no sneezing or nasal rubbing. In addition, prostaglandin D 2 also showed no significant increase in these responses, even at a dose of 10 nmol/site. On the other hand, the simultaneous instillation of histamine and prostaglandin D 2 resulted in a 1000 times more potent effect in inducing nasal symptoms than the administration of histamine alone. Thus, prostaglandin D 2 enhanced the actions of histamine in inducing sneezing and nasal rubbing in a dose-dependent manner, and significant effects were observed at doses higher than 1 nmol/site. The responses induced by the simultaneous application of histamine and prostaglandin D 2 were inhibited by chlorpheniramine, cyproheptadine, BW A868C and ramatroban. Chlorpheniramine and cyproheptadine showed the dose-related inhibition of nasal symptoms induced by the combined administration of histamine (10 nmol) and prostaglandin D 2 (10 nmol), but the effect of cyproheptadine was relatively weak compared with chlorpheniramine. Moreover, BW A868C and ramatroban also showed the inhibition of nasal symptoms induced by the simultaneous administration of histamine and prostaglandin D 2 in a dose-dependent manner. BW A868C was more potent in inhibiting the nasal symptoms than ramatroban. These results clearly indicate that prostaglandin D 2 showed a synergistic effect on sneezing and nasal rubbing induced by histamine in rats, and its effect occurred through both prostaglandin D 2 and CRTH2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) receptors.

Serotonin-Related Enhancement of Recovery of Hind Limb Motor Functions in Spinal Rats after Grafting of Embryonic Raphe Nuclei

Recently, we demonstrated improvements in hind limb locomotor-like movements following grafting of embryonic raphe nuclei cells into the spinal cord below the level of total transection in adult rats. The purpose of the present study was to clarify whether this improvement was due to newly established serotonergic innervation between the graft and the host. Two months after intraspinal grafting of the embryonic raphe nuclei, the spinalized rats, when put on a treadmill, could be induced to walk with regular alternating hind limb movements with the plantar contact with the ground during the stance phase, and ankle dorsiflexion during the swing phase of each step cycle. In the same situation the spinal rats, that did not receive the graft, were not able to initiate the dorsiflexion of the ankle joint during the swing phase and very often the dorsal surface of the foot was dragged along the ground. Intraperitoneal application of directly acting 5-HT2 antagonist Cyproheptadine (1 mg/kg) impaired reversibly the hind limb locomotor-like movements in grafted rats. This impairment lasted for 2-3 h. The same procedure in control rats did not markedly alter the hind limb locomotor-like movements. The effect of Cyproheptadine in grafted rats was reversed by i.p. injections of the 5-HT2 agonist Quipazine (0.5 mg/kg). These results show that the graft-induced restitution of hind limb locomotor abilities in adult spinal rats is brought about by the new serotonergic innervation of the host spinal cord circuitry from the grafted neurons and is mediated by 5-HT2 receptors.

MRI Findings and Effectiveness of Cyproheptadine in Two Patients with Ophthalmoplegic Migraine

MRI Findings and Effectiveness of Cyproheptadine in Two Patients with Ophthalmoplegic Migraine

Effects of cyproheptadine clorhydrate ,a serotonin receptor antagonist ,on endocrine parameters in weight-loss related amenorrhea

The aim of the study was to evaluate the possible interactions and/or modulations of the serotoninergic system on hormonal parameters and the reproductive axis in amenorrheic subjects. Hypogonadotropic,underweight ,amenorrheic patients (n = 8) were studied before and during cyproheptadine clorhydrate administration (4 mg/day for 3 months). A pulsatility study (4 hours ,sampling every 10 minutes) and analoxone test were performed before and after 4 and 12 weeks of treatment. Plasma luteinizing hormone (LH) ,follicle-stimulating hormone (FSH) ,growth hormone (GH) ,estradiol ,thyroid-stimulating hormone(TSH) ,free tri-iodothyronine (fT3) ,free thyroxine (fT4) and total triiodothyonine (total T3) ,insulin-like growth factor-I (IGF-I) concentrations were determined. Pulsedetection analysis was performed using the DETECT program.Serotoninergic receptor blockade affected neither the naloxone-inducted LH response nor the gonadotropin pulsatile parameters. Body mass index(BMI) did not vary; conversely ,integrated mean gonadotropins ,GH and fT3 concentrations increased during the treatment. In conclusion ,cyproheptadine administration affects some of the abnormalendocrine parameters of underweight amenorrheic subjects with no modulation of the opioidergic system. It is likely that the gonadotropin and the fT3 increases take place owing to a change inthe metabolic signals modulating hypothalamic function and/or an increased energy availability. Our study suggests a specific central effect of cyproheptadine on the serotonergic pathway controlling foodintake at the hypothalamic level.

Suppressive effects of antihistaminic and/or anti-PAF agents on passive anaphylactic shock in mice sensitized with allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum

For the immunopharmacological characterization of murine passive anaphylactic shock, the effects of antihistaminics and/or anti-platelet-activating factor (anti-PAF) agents were studied on the shock mediated by allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum. IgE antibody-mediated shock was strongly suppressed by cyproheptadine (10 mg/kg, ip) in every strain regardless of the age and sex of the mice and the presence or absence of a shock potentiator. As far as tested with CTS, DS, and B6D2F1 mice, IgE antibody-mediated shock was also suppressed by the other two antihistamines, triprolidine (10 mg/kg, ip) and oxatomide (100 mg/kg, Po). This type of shock was not suppressed by an anti-PAF agent, CV-6209 (3.3 mg/kg, iv), when tested on aged CTS mice given no shock potentiator and young DS mice given a potentiator such as Bordetella pertussis organisms or DL-propranolol. IgG1 antibody-mediated shock was also suppressed by cyproheptadine in general except for CTS mice. Suppression in the DL-propranolol-treated DS and C3H/He mice was not very marked on sensitization with undiluted or slightly diluted IgG1 ascites but quite striking on sensitization with properly diluted ascites. In contrast with the effect of cyproheptadine, suppression by CV-6209 was obvious in aged CTS mice but not in young DL-propranolol-treated DS mice. The shock in DL-propranolol-treated DS mice sensitized with undiluted or slightly diluted ascites was completely abolished by the combined use of these two agents. These results suggest that histamine and/or PAF play a major role in IgE antibody- and IgG1 antibody-mediated shock. However, so far as tested in young DS mice, the shock mediated by serum differed in drug susceptibility from that mediated by the monoclonal antibodies. In the absence of shock potentiators, prevention was produced by cyproheptadine in the males which had been sensitized with the 1:4 or 1:8 dilution of the immune serum. In the presence of DL-propranolol, prevention was not produced even by the combined treatment with cyproheptadine and CV-6209. Therefore, it is likely that some mediators other than histamine and PAF, whose release is triggered by antibody isotypes other than IgE and IgG1, play a greater role for the shock mediated by hyperimmune serum than for the shock mediated by IgE or IgG1 antibody, especially in the presence of shock potentiators.

Luteinizing hormone and ovarian response of early postpartum Debouillet ewes treated with cyproheptadine and(or) melatonin.

Two trials were conducted to evaluate the effects of cyproheptadine (serotonin receptor antagonist, Trial 1) along with administering melatonin (Trial 2) to early postpartum (PP) ewes on LH profiles and follicular development. In Trial 1, 12 mature ewes received either control (CON) or cyproheptadine (CYP) treatments (six ewes/treatment). Beginning on d 5 PP, each ewe received i.v. either 0 (vehicle) or .1 mg of CYP/kg BW twice daily for 5 d. Cyproheptadine tended to stimulate (P < .10) release of LH on d 5 PP (1.3 and .8 +/- .2 ng LH/mL for CYP-treated and CON ewes, respectively) with a similar trend (P < .10) of LH release occurring on d 9. Cyproheptadine also had a positive effect on follicular development, but no luteal activity was detected. In Trial 2, 16 mature ewes received CON, i.v. CYP (.1 mg/kg BW twice daily), i.m. melatonin (MEL, 5 mg x ewe(-1) x d(-1)), or CYP+MEL. Treatments were administered from d 5 through 14 PP. Cyproheptadine tended to increase (P < .10) LH pulsatility on d 5 and 14, but MEL had no effect (P > .20). Follicular development was not affected (P > .40) by CYP or MEL treatments. Neither MEL nor CYP affected progesterone (P > .60). Cyproheptadine tended to increase LH concentration and pulse frequency in early PP ewes, but MEL had no effect on LH profiles. Both treatments failed to initiate ovarian cyclicity in early PP ewes.

THE EFFECT OF CYPROHEPTADINE AND AMANTADINE ON NEUROLEPTIC-INDUCED CATALEPSY IN THE RAT

Catalepsy is not a unitary phenomenon. With respect to biochemical mechanisms and neurotransmitter sytems, the origin of this behavioural response varies according to different substances which cause catalepsy. For example, the catdeptogenic effect of neuroleptics has been related to the blockage of striatal doparnine receptors. Neurophysiological and biochemical data have shown that a mechanism caused by gama-aminobutyric acid and serotonin have been effective in the proper functioning of the dopaminergic nigrosbriatal tract. We have studied the effects of cyproheptadine, a serotonin antagonist, and of amantadin which is used in the treatment of Parkinson syndrome on the catalepsy induced by trifluoperazine, a phenothiazin compound, and pimozid, a drug used as a neuroleptic. It was observed that when rats were pretreated with cyproheptadine as well as amantadine, the catalepsy induced by the above neuroleptic drugs was attenuated. The results of our study show that substances which have an effect on the serotonergic and dopaminergic systems also play a role on cases of catalepsy induced by the neuroleptic drugs mentioned above. Key words: Catalepsy, neuroleptic, cyproheptadine, amantadine.

Protective effects of cyproheptadine on cisplatin-induced adverse effects in digestive tracts in patients with primary lung cancer

Protective effects of cyproheptadine on cisplatin-induced adverse effects in digestive tracts in patients with primary lung cancer

The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries.

The effects of cyproheptadine, a serotonergic antagonist, were studied in seven patients with spastic paresis of spinal origin. Six patients were included in a double blind crossover trial (maximal dose 24 mg/day). The patients were evaluated on both their spasticity and locomotor function. Four of the patients also participated in an open trial in which cyproheptadine was administered for a minimum of six months at optimal dose. Patients walked on a treadmill at full weight bearing when possible, or with 40% of their body weight externally supported, as required, by an overhead harness system. Cyproheptadine considerably decreased the sustained ankle clonus and episodes of spontaneous spasms observed in all the patients who previously presented these manifestations of spasticity. Two patients who required body weight support (BWS) during locomotion could walk at full weight bearing during cyproheptadine therapy. A more normal timing of EMG patterns in these patients during cyproheptadine therapy was associated with temporal distance changes and marked improvement of joint angular displacement. In contrast, the other patients showed marginal changes in the EMG and the kinematic pattern but eventually managed to walk at a higher speed. These preliminary results suggest that cyproheptadine can reduce spasticity and enhance locomotor function in spinal cord injured patients.