Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) 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 instantaneous 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 mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I 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 I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.
Animals ; Cyproheptadine ; pharmacology ; Female ; Histamine H1 Antagonists ; pharmacology ; Membrane Potentials ; drug effects ; physiology ; Mice, Inbred C57BL ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Prefrontal Cortex ; drug effects ; physiology ; Pyramidal Cells ; drug effects ; physiology ; Receptors, sigma ; agonists ; metabolism ; Tetraethylammonium ; pharmacology ; Tissue Culture Techniques

Anorexia is one of the most common issues in older patients. Although there is a tendency for loss of appetite in older persons due to decreased physical activity and reduced resting metabolic rate, this physiological anorexia of aging can easily develop into progressive anorexia and weight loss. This pathologic anorexia and resultant weight loss is associated with increased morbidity and mortality, especially in the frail elderly. To prevent older persons from entering a vicious cycle of frailty, that is, anorexia-malnutrition-sarcopenia-functional impairment, routine screening for anorexia and malnutrition should be implemented in geriatric clinical practice. All anorexic elderly patients should be strongly encouraged to maintain their nutrition, and appetite stimulants can be considered if non-pharmacological interventions are not effective. Although there are no US or Korea Food and Drug Administration approved medications for geriatric-specific anorexia and weight loss, several appetite stimulants can be prescribed and are used widely. Megestrol acetate is the most widely studied and commonly used of these drugs. Cyproheptadine, dronabinol, mirtazapine, corticosteroids, anabolic steroids (e.g., testosterone or oxandrolone), and growth hormone are also effective in increasing appetite or weight. However, the use of these orexigenic agents should occur only after their benefit-to-risk ratio has been carefully considered.
Adrenal Cortex Hormones ; Aged ; Aging ; Anorexia ; Appetite Stimulants* ; Appetite* ; Cyproheptadine ; Diethylpropion ; Dronabinol ; Frail Elderly ; Growth Hormone ; Humans ; Korea ; Malnutrition ; Mass Screening ; Megestrol Acetate ; Mortality ; Motor Activity ; Steroids ; Testosterone ; United States Food and Drug Administration ; Weight Loss

Cyclic vomiting syndrome (CVS) is a functional disorder characterized by stereotypical episodes of intense vomiting separated by weeks to months. Although it can occur at any age, the most common age at presentation is 3-7 years. There is no gender predominance. The precise pathophysiology of CVS is not known but a strong association with migraine headaches, in the patient as well as the mother indicates that it may represent a mitochondriopathy. Studies have also suggested the role of an underlying autonomic neuropathy involving the sympathetic nervous system in its pathogenesis. CVS has known triggers in many individuals and avoiding these triggers can help prevent the onset of the episodes. It typically presents in four phases: a prodrome, vomiting phase, recovery phase and an asymptomatic phase until the next episode. Complications such as dehydration and hematemesis from Mallory Wise tear of the esophageal mucosa may occur in more severe cases. Blood and urine tests and abdominal imaging may be indicated depending upon the severity of symptoms. Brain magnetic resonance imaging and upper gastrointestinal endoscopy may also be indicated in certain circumstances. Management of an episode after it has started ('abortive treatment') includes keeping the patient in a dark and quiet room, intravenous hydration, ondansetron, sumatriptan, clonidine, and benzodiazepines. Prophylactic treatment includes cyproheptadine, propranolol and amitriptyline. No mortality has been reported as a direct result of CVS and many children outgrow it over time. A subset may develop other functional disorders like irritable bowel syndrome and migraine headaches.
Amitriptyline ; Benzodiazepines ; Brain ; Child ; Clonidine ; Cyproheptadine ; Dehydration ; Endoscopy, Gastrointestinal ; Hematemesis ; Humans ; Irritable Bowel Syndrome ; Magnetic Resonance Imaging ; Migraine Disorders ; Mortality ; Mothers ; Mucous Membrane ; Ondansetron ; Propranolol ; Sumatriptan ; Sympathetic Nervous System ; Vomiting*

Cancer-related anorexia-cachexia syndrome (CACS) is a hypercatabolic state, characterized by reduced appetite and weight loss due to ongoing loss of skeletal muscle mass and adipose tissue. CACS occurs mainly in patients with advanced cancer; thus, weight loss in CACS is often associated with poor prognosis and decreased survival. A large number of studies have been conducted on various pharmacologic agents for palliation of cancer-related anorexia. The purpose of this article is to review the pre-existing pharmacologic agents used for CACS and to evaluate the evidence from current studies on each pharmacologic agent. First, appetite stimulants such as corticosteroids, progestins, cyproheptadine, and cannabinoid have been shown to be beneficial by improving appetite and helping with weight changes even if they had no effect on survival rate. Several other agents with anti-inflammatory effects (e.g., eicosapentaenoic acid, thalidomide, and melatonin), prokinetic agents (e.g., metoclopramide), anabolic agents (e.g., androgens and growth hormone), antipsychotics (e.g., mirtazapine and olanzapine), and antiemetics have also been studied in patients in CACS; however further investigations would be required to confirm the beneficial effects.
Adipose Tissue ; Adrenal Cortex Hormones ; Anabolic Agents ; Androgens ; Anorexia ; Antiemetics ; Antipsychotic Agents ; Appetite ; Appetite Stimulants ; Cachexia ; Cyproheptadine ; Eicosapentaenoic Acid ; Glucocorticoids ; Humans ; Muscle, Skeletal ; Progestins ; Prognosis ; Survival Rate ; Thalidomide ; Weight Loss

OBJECTIVETo search for an effective therapy for cold erythema multiforme in ham.

METHODSOne hundred and eighty cases with cold erythema multiforme in ham were randomly divided into a Santong group (n=90) and a western medicine group (n=90). The Santong group was treated by He's Santong needling methods and Huantiao (GB 30), Fengshi (GB 31), Zusanli (ST 36), etc. were selected. The western medicine group was treated by oral administration of Cinnarizine, Cyproheptadine and Vitamin E. Two weeks later, their therapeutic effects were observed.

RESULTSThe cured rate was 68.9% and the recurrence rate was 11.3% in the Santong group, and 33.3% and 53.3% in the western medicine group, with significant differences in the cured rate and the recurrence rate between the two groups (both P<0.01).

CONCLUSIONHe's Santong needling methods can increase the cured rate and reduce the recurrence rate of cold erythema multiforme in ham.

Acupuncture Therapy ; Adolescent ; Adult ; Cinnarizine ; therapeutic use ; Cyproheptadine ; therapeutic use ; Erythema Multiforme ; drug therapy ; therapy ; Female ; Histamine H1 Antagonists ; therapeutic use ; Humans ; Male ; Treatment Outcome ; Young Adult

Acute lung injury (ALI) makes up a spectrum of disease that is commonly defined as "acute non-cardiogenic edematous lung injury". It may contribute to morbidity and mortality in the critically ill patient in the intensive care unit. ALI was induced by oleic acid in rabbits. During the experiment, blood samples were taken from cervical artery and subjected to blood-gas analysis at different time points after oleic acid injection. Shortly after the rabbits were killed at 3 hour after iv OA injection, bronchoalveolar lavage fluid (BALF) was colleted, and the concentrations of protein, platelet-activating factor (PAF), intercellular adhesion molecule-1 (ICAM-1), interleukin 8 (IL-8) in BALF were then measured by ELISA. The ratio of wet to dry weight (W/D) of left lung was calculated to assess alveolar edema. Lung tissue was fixed in formaldehyde and stained with HE, and examined under a light microscope. The OA-induced elevation of arterial blood oxygen pressure was inhibited, as well as PAF, ICAM-1, IL-8 in BALF in rupatadine group. Furthermore, rupatadine also decreased the concentration of protein in BALF and inhibited the increase of the W/D weight ratio significantly. Light microscopic findings showed that the damage in rupatadine groups was far less severe than that in OA model group. Pretreatment with rupatadine has a beneficial effect on acute lung injury induced by oleic acid in rabbits. The ultimate reduction of inflammatory factors was involved, at least in part, in the mechanism of action of rupatadine effects.
Animals ; Blood Gas Analysis ; Bronchoalveolar Lavage Fluid ; chemistry ; Cyproheptadine ; analogs & derivatives ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-8 ; metabolism ; Lung ; drug effects ; metabolism ; pathology ; Male ; Oleic Acid ; Platelet Activating Factor ; metabolism ; Protective Agents ; pharmacology ; Rabbits ; Random Allocation ; Respiratory Distress Syndrome, Adult ; chemically induced ; metabolism ; prevention & control

AIMTo explore the modulation of 5-HT on GABA-activated current (I(GABA)) in the membrane of rat dorsal root ganglion (DRG) neurons and its mechanism.

METHODSRat DRG neurons were isolated mechanically and enzymatically, on which whole-cell patch clamp recording and repatch technique for intracellular dialysis were performed.

RESULTSIn the majority of neurons examined (92.0%, 69/75) GABA induced a concentration-dependent inward current. In neurons sensitive to GABA preapplication of 5-HT produced potentiation effect (82.6% , 57/69) on I(GABA). Preapplication of 5-HT at concentrations of 1 x 10(-6), 1 x 10(-5), 1 x 10(-4) and 1 x 10(-3) mol x L(-1) potentiated I(GABA) by (35 +/- 8)% (n=8), (47 +/- 11)% (n=10), (65 +/- 17)% (n=9) and (75 +/- 18)% (n=11), respectively. This effect was mimicked by alpha-methyl-5-HT (1 x 10(-6) mol x L(-1)), a specific 5-HT2 receptor agonist, and reversed by cyproheptadine, a selective 5-HT2 receptor antagonist. The potentiation of I(GABA) by 5-HT was irrespective to whether the I(5-HT) presents or not in a subset of neurons. The concentration-response curves for GABA before and after pretreatment with 5-HT manifested the same threshold value and similar EC50 (2.0 x 10(-5) and 1.9 x 10(-5) mol x L(-1), respectively) , while the maximal value of I(GABA) for the latter was 33.6% higher than that for the former. Intracellular dialysis with GDP-beta-S or H-7 abolished the potentiation of I(GABA) by 5-HT, while H-9 did not.

CONCLUSION5-HT can potentiate GABA-activated current via PKC-dependent phosphorylation of GABA(A) receptor following the activation of 5-HT2 receptor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; pharmacology ; Animals ; Cyproheptadine ; pharmacology ; Female ; Ganglia, Spinal ; cytology ; physiology ; Male ; Membrane Potentials ; drug effects ; Neurons ; physiology ; Patch-Clamp Techniques ; Protein Kinase C ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT2 ; Serotonin ; analogs & derivatives ; pharmacology ; Serotonin 5-HT2 Receptor Agonists ; Serotonin 5-HT2 Receptor Antagonists ; Signal Transduction ; gamma-Aminobutyric Acid ; pharmacology

OBJECTIVETo investigate the antagonistic effect and mechanism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats.

METHODSEndotoxic shock was produced in rats by i.v. injection of lipopolysaccharides (LPS) (5 mg/kg). Tumor necrosis factor (TNF(alpha)) mRNA expression was assessed by Northern blot. Plasma TNF(alpha) content was measured by radioimmunoassay. Plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. The intracellular free calcium concentration ([Ca(2+)](i)) in single endothelial cells was determined by laser scanning confocal microscopy (LSCM).

RESULTSCyp 5 mg/kg injected immediately after i.v. LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24 h survival rate. Meanwhile, Cyp markedly decreased TNF(alpha) mRNA levels in rat liver (18 +/- 10 vs. LPS + saline 38 +/- 10, P < 0.01) as well as plasma TNF(alpha) content [(7.8 +/- 2.4) microg/L vs. LPS + saline (21.5 +/- 3.2) microg/L, P < 0.01)]. It enhanced plasma SOD activity [(1037.2 +/- 112.8) NU/L vs LPS + saline (615.4 +/- 92.6) NU/L, P < 0.01], reduced the MDA content [(5.2 +/- 1.1) micromol/L vs. LPS + saline (9.8 +/- 1.5) micromol/L, P < 0.01], and inhibited TNF(alpha)-induced [Ca(2+)](i) elevation.

CONCLUSIONCyp exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca(2+)](i) overload.

Animals ; Cyproheptadine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Malondialdehyde ; blood ; Rats ; Rats, Wistar ; Shock, Septic ; drug therapy ; metabolism ; Superoxide Dismutase ; blood ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics

Effects of serotonin (5-HT) on spontaneous discharges of single hypothalamic arcuate neurons were observed in rat brain slices by extracellular recordings. The results showed that (1) of 149 neurons selected randomly and tested for 5-HT application, 33 (22.2%) were excited, 82 (55.0%) were inhibited, and 34 (22.8%) showed biphasic responses or failed to respond; (2) substitution of low Ca(2+)-high Mg(2+) artificial cerebrospinal fluid (aCSF) for normal aCSF abolished the 5-HT-induced inhibitory effect but failed to affect the 5-HT-induced excitatory effect; (3) cyproheptadine, a non-selective 5-HT receptor antagonist, could block either the 5-HT-induced excitatory or inhibitory effects in all neurons tested; and (4) bicuculline, a GABA(A)-receptor antagonist, blocked the 5-HT-induced inhibitory effect. These results imply (1) 5-HT excites arcuate neurons through a mechanism that is insensitive to the decreased extracellular Ca(2+), suggesting a direct postsynaptic action of 5-HT on the 5-HT-receptors located in the membrane of the neurons recorded; and (2) 5-HT might elicit the inhibitory effect through a Ca(2+)-sensitive release of GABA from intercalated GABAergic local neurons that are excited first by 5-HT.
Animals ; Arcuate Nucleus of Hypothalamus ; drug effects ; physiology ; Cyproheptadine ; pharmacology ; In Vitro Techniques ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar ; Serotonin ; pharmacology ; gamma-Aminobutyric Acid ; physiology

A 54-year-old male patient who was suffering from bipolar I disorder for 19 years and was admitted to the National Bugok Mental Hospital due to a depressive episode, was referred to the Kosin University Gospel Hospital. On arrival at the emergency room, he had confused mentality with disorientation, memory impairment, hypomania, marked anxiety and hyperirritability. The change of neuromuscular activity such as ataxia, gait disturbance, tremor, shivering, myoclonus and epileptic seizures was also shown. In addition, the symptoms and signs of autonomic instability including diaphoresis, tachycardia, hypotension, fever and facial flushing were noticed. The above symptoms developed after the administration of sertraline successive to the discontinuation of fluoxetine without any washout period. The degree of severity seemed to be severe because he had epileptic seizures, fever and hypotension. He was recovered from the severe serotonin syndrome by the supportive symptomatic treatment with sodium valproate, clonazepam, lorazepam and cyproheptadine after cessation of the selective serotonin reuptake inhibitors during hospitalization. Therefore, this rare case of severe serotonin syndrome was reported and related literatures were also reviewed.
Anxiety ; Clonazepam ; Cyproheptadine ; Emergency Service, Hospital ; Epilepsy ; Fever ; Fluoxetine* ; Flushing ; Gait Ataxia ; Hospitalization ; Hospitals, Psychiatric ; Humans ; Hypotension ; Lorazepam ; Male ; Memory ; Middle Aged ; Myoclonus ; Serotonin Syndrome* ; Serotonin Uptake Inhibitors ; Serotonin* ; Sertraline* ; Shivering ; Tachycardia ; Tremor ; Valproic Acid