Changes of 5-hydroxytryptamine(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)levels in brain cortex and serum were studied using spectrofluorometer follow-ing brain injury in rats.Cyproheptadine,a receptor antagonist of ...Changes of 5-hydroxytryptamine(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)levels in brain cortex and serum were studied using spectrofluorometer follow-ing brain injury in rats.Cyproheptadine,a receptor antagonist of 5-HT,was employedand its effect on alterations of 5-HT and 5-HIAA contents in brain cortex and serum af-ter brain injury was investigated.The results showed that after brain injury levels of5-HT and 5-HIAA in the brain cortex increased markedly,The increase of 5-HT in thebrain cortex reached its peak at 48h after brain injury,and its value was 4.29±0.44μg/g,which was 4.8 times of control value.The increase of 5-HIAA in the brain cortexreached its peak at 24h after brain injury,and its value was 5.48±0.41μg/g,which was5.8times of control value.The change of 5-HT in the serum was not significant,but thelevel of 5-HIAA in the serum was increased significantly.Cyproheptadine could reducelevels of 5-HT and 5-HIAA in this experiment.The value of 5-HT in the brain cortexdecreased to 1.32±0.09μg/g,and the value of 5-HIAA decreased to 1.36±0.10μg/g.Thelevel of 5-HIAA in the serum was also reduced significantly.It was 0.27±0.03μg/ml.展开更多
Experiments were performed on 25 rats. Putative serotonergic antagonist, Cyproheptadine(Cyp), was applied microiontophoretically on the nucleus parafascicularis of the thalamus (Pf) andthe effect of Cyp on Pf nocicept...Experiments were performed on 25 rats. Putative serotonergic antagonist, Cyproheptadine(Cyp), was applied microiontophoretically on the nucleus parafascicularis of the thalamus (Pf) andthe effect of Cyp on Pf nociceptive neuronal discharge was observed. The result suggested that Cypcan increase the spontaneous and evoked discharge rates of Pf nociceptive neuron, and that Cypmay antagonize the inhibitory effect of endogenous serotonin on the spontaneous and evokeddischarges of Pf nociceptive neurons.展开更多
Acute traumatic brain edema models were established in SD rats by dropping weight methods.We observed the therapeutic effect of Cyproheptadine(Cyp)on traumatic brain edema.It was shown that Cyp could obviously reduce ...Acute traumatic brain edema models were established in SD rats by dropping weight methods.We observed the therapeutic effect of Cyproheptadine(Cyp)on traumatic brain edema.It was shown that Cyp could obviously reduce the brain water content,decrease the releae or LDH,reduce the seventy of the pathological changes at the injury areas,increase the SOD activity and decrease the production of MDA in SD rats.The results suggest that Cyp has obvious.therapeutic effect on traumatic brain edema.The mechanism may be that it can increase the activity or clearance enzyme of free radical,inhibit lipid peroxldation and reduce intracellular Ca2+-overload.展开更多
Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it ...Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.展开更多
Profound hemorrhagic shock was produced in thirty rabbits by exsanguination via the carotid artery until blood pressure (BP) reached 5.3 kPa (40 mmHg) and was sustained for a period of 90 minutes. The rabbits were equ...Profound hemorrhagic shock was produced in thirty rabbits by exsanguination via the carotid artery until blood pressure (BP) reached 5.3 kPa (40 mmHg) and was sustained for a period of 90 minutes. The rabbits were equally divided into cyproheptadine (Cyp) treated group and control group. Blood samples 30 minutes after liquid and blood infusion and administration of Cyp (10 mg / kg) were collected from the carotid artery, and the plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content measured. The results showed that Cyp remarkebly enhanced the plasma SOD activity (2462 338 vs 1955- 596, P<0.01) and reduced MDA content (2.68- 0.24 vs 3.20-0.49, P<0.01). We believe that the in crease of O2 production plays an important role in the develop-ment of shock, the single blood and liquid infusion can not significantly improve the shock conditions. Scavenging oxygen free radicals and alleviating cellular damage and multiple or gan failure are the possible mechanisms of cyproheptadine anti-shock effect.展开更多
Cyproheptadine （CPH）, a first-generation anti- histamine, enhances the delayed rectifier outward K＋ current （IK） in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this stu...Cyproheptadine （CPH）, a first-generation anti- histamine, enhances the delayed rectifier outward K＋ current （IK） in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH （10 μmol/L） significantly reduced the current density required to generate action potentials （APs） and increased the instan- taneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential （RMP）, decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mim- icked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium （TEA） to block IK channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive IK channels as well as other TEA-insensitive K＋ channels, probably ID and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.展开更多
Like electroacupuncture (EA),electrical stimulation of the dorsal raphe nucle-us (DRN)also inhibits the cAMP induced cortical epileptic waves and the EA inducedinhibition can be abolished or markedly reduced by iv cyp...Like electroacupuncture (EA),electrical stimulation of the dorsal raphe nucle-us (DRN)also inhibits the cAMP induced cortical epileptic waves and the EA inducedinhibition can be abolished or markedly reduced by iv cyproheptadine (CYP) or destruc-tion of DRN by electrolysis.The results suggest that 5-HT neurons in the DRN mayplay an important role in the EA inhibition of the generation of cAMP induced elec-trocorticogram (ECoG) epileptic waves.展开更多
BACKGROUND Serotonin syndrome(SS)is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin.Very limited information is available about chronic SS.AIM To eva...BACKGROUND Serotonin syndrome(SS)is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin.Very limited information is available about chronic SS.AIM To evaluate the epidemiological,clinical,and other aspects of the insidious onset SS.METHODS We retrospectively evaluated 14 consecutive adult patients(>18 years)who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS.RESULTS The mean age was 41.1 years(range:21-61 years),with a male preponderance(64%).Although tremors were observed in all patients,this was a presenting complaint in only 43%of patients.Generalized body pain,insomnia,and restlessness were common presenting features(50%each).Other common clinical features were stiffness of the limbs(43%),diaphoresis(43%),gait disturbances(36%),bowel disturbances(36%),dizziness(29%),sexual dysfunctions(21%),incoordination(14%),and fatigue(14%)The mean duration of symptoms before the diagnosis of SS was 13.5±5.8 wk(range:6-24 wk).Amitriptyline was the most common drug(n=6,43%),followed by tramadol(n=5,36%)and sodium valproate(n=5,36%).All patients received cyproheptadine,a 5-hydroxytryptamine2A antagonist,as treatment and noted an excellent response CONCLUSION This study represents the largest study on chronic SS.We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.展开更多
文摘Changes of 5-hydroxytryptamine(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)levels in brain cortex and serum were studied using spectrofluorometer follow-ing brain injury in rats.Cyproheptadine,a receptor antagonist of 5-HT,was employedand its effect on alterations of 5-HT and 5-HIAA contents in brain cortex and serum af-ter brain injury was investigated.The results showed that after brain injury levels of5-HT and 5-HIAA in the brain cortex increased markedly,The increase of 5-HT in thebrain cortex reached its peak at 48h after brain injury,and its value was 4.29±0.44μg/g,which was 4.8 times of control value.The increase of 5-HIAA in the brain cortexreached its peak at 24h after brain injury,and its value was 5.48±0.41μg/g,which was5.8times of control value.The change of 5-HT in the serum was not significant,but thelevel of 5-HIAA in the serum was increased significantly.Cyproheptadine could reducelevels of 5-HT and 5-HIAA in this experiment.The value of 5-HT in the brain cortexdecreased to 1.32±0.09μg/g,and the value of 5-HIAA decreased to 1.36±0.10μg/g.Thelevel of 5-HIAA in the serum was also reduced significantly.It was 0.27±0.03μg/ml.
文摘Experiments were performed on 25 rats. Putative serotonergic antagonist, Cyproheptadine(Cyp), was applied microiontophoretically on the nucleus parafascicularis of the thalamus (Pf) andthe effect of Cyp on Pf nociceptive neuronal discharge was observed. The result suggested that Cypcan increase the spontaneous and evoked discharge rates of Pf nociceptive neuron, and that Cypmay antagonize the inhibitory effect of endogenous serotonin on the spontaneous and evokeddischarges of Pf nociceptive neurons.
文摘Acute traumatic brain edema models were established in SD rats by dropping weight methods.We observed the therapeutic effect of Cyproheptadine(Cyp)on traumatic brain edema.It was shown that Cyp could obviously reduce the brain water content,decrease the releae or LDH,reduce the seventy of the pathological changes at the injury areas,increase the SOD activity and decrease the production of MDA in SD rats.The results suggest that Cyp has obvious.therapeutic effect on traumatic brain edema.The mechanism may be that it can increase the activity or clearance enzyme of free radical,inhibit lipid peroxldation and reduce intracellular Ca2+-overload.
文摘Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.
文摘Profound hemorrhagic shock was produced in thirty rabbits by exsanguination via the carotid artery until blood pressure (BP) reached 5.3 kPa (40 mmHg) and was sustained for a period of 90 minutes. The rabbits were equally divided into cyproheptadine (Cyp) treated group and control group. Blood samples 30 minutes after liquid and blood infusion and administration of Cyp (10 mg / kg) were collected from the carotid artery, and the plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content measured. The results showed that Cyp remarkebly enhanced the plasma SOD activity (2462 338 vs 1955- 596, P<0.01) and reduced MDA content (2.68- 0.24 vs 3.20-0.49, P<0.01). We believe that the in crease of O2 production plays an important role in the develop-ment of shock, the single blood and liquid infusion can not significantly improve the shock conditions. Scavenging oxygen free radicals and alleviating cellular damage and multiple or gan failure are the possible mechanisms of cyproheptadine anti-shock effect.
基金supported by the National Natural Science Foundation of China(31370827)the Shanghai Leading Academic Discipline Project [B111]
文摘Cyproheptadine （CPH）, a first-generation anti- histamine, enhances the delayed rectifier outward K＋ current （IK） in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH （10 μmol/L） significantly reduced the current density required to generate action potentials （APs） and increased the instan- taneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential （RMP）, decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mim- icked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium （TEA） to block IK channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive IK channels as well as other TEA-insensitive K＋ channels, probably ID and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.
文摘Like electroacupuncture (EA),electrical stimulation of the dorsal raphe nucle-us (DRN)also inhibits the cAMP induced cortical epileptic waves and the EA inducedinhibition can be abolished or markedly reduced by iv cyproheptadine (CYP) or destruc-tion of DRN by electrolysis.The results suggest that 5-HT neurons in the DRN mayplay an important role in the EA inhibition of the generation of cAMP induced elec-trocorticogram (ECoG) epileptic waves.
文摘BACKGROUND Serotonin syndrome(SS)is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin.Very limited information is available about chronic SS.AIM To evaluate the epidemiological,clinical,and other aspects of the insidious onset SS.METHODS We retrospectively evaluated 14 consecutive adult patients(>18 years)who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS.RESULTS The mean age was 41.1 years(range:21-61 years),with a male preponderance(64%).Although tremors were observed in all patients,this was a presenting complaint in only 43%of patients.Generalized body pain,insomnia,and restlessness were common presenting features(50%each).Other common clinical features were stiffness of the limbs(43%),diaphoresis(43%),gait disturbances(36%),bowel disturbances(36%),dizziness(29%),sexual dysfunctions(21%),incoordination(14%),and fatigue(14%)The mean duration of symptoms before the diagnosis of SS was 13.5±5.8 wk(range:6-24 wk).Amitriptyline was the most common drug(n=6,43%),followed by tramadol(n=5,36%)and sodium valproate(n=5,36%).All patients received cyproheptadine,a 5-hydroxytryptamine2A antagonist,as treatment and noted an excellent response CONCLUSION This study represents the largest study on chronic SS.We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.
