化工社化工社 化学情報印刷レポート · 研究参考用
シプロヘプタジン
4-(5H-ジベンゾ[a,d]シクロヘプテン-5-イリデン)-1-メチルピペリジン · ペリアクチン · 4-[5H-ジベンゾ[a,d]シクロヘプテン-5-イリデン]-1-メチルピペリジン · シプロヘプタジン · 5-(1-メチルピペリジン-4-イリデン)-5H-ジベンゾ[a,d]シクロヘプテン · ペリアクチノール · サイプロヘプタジン · 1-メチル-4-{トリシクロ[9.4.0.03,8]ペンタデカ-1(15),3,5,7,9,11,13-ヘプタエン-2-イリデン}ピペリジン
識別子と物理属性
| CAS No. | 129-03-3 |
|---|---|
| 分子式 | C21H21N |
| 平均分子量 | 287.4 g/mol |
| 単同位体質量 | 287.16739967 g/mol |
| SMILES | CN1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1 |
| InChIKey | JJCFRYNCJDLXIK-UHFFFAOYSA-N |
| PubChem CID | 2913 |
| ChEMBL | CHEMBL516 |
| ChEBI | CHEBI:4046 |
| EC No. | 204-928-9 |
| DTXSID | DTXSID8022872 |
| 現地名 | シプロヘプタジン |
化学・物理的性質
| XLogP | 4.7 |
|---|---|
| 極性表面積 | 3.2 |
| 水素結合供与体数 | 0 |
| 水素結合受容体数 | 1 |
| 回転可能結合数 | 0 |
| 重原子数 | 22 |
| 形式電荷 | 0 |
| 複雑度 | 423 |
| LogP（分配係数） | 4.69Log P= 4.694.7 |
| Color/Form | CRYSTALS FROM DIL ETHANOL |
| 溶解度 | WHITE TO SLIGHTLY YELLOW, CRYSTALLINE POWDERODORLESSSLIGHT BITTER TASTENONHYGROSCOPIC1 G SOL IN 1.5 ML METHANOL, 16 ML CHLOROFORM, 35 ML ALCOHOL, 275 ML WATERPRACTICALLY INSOL IN ETHER /HCL/1.36e-02 g/L317.6ug/L(22.5℃) |
| 融点 | 112.3-113.3112.3-113.3 °C215 - 217 °C112.3-113.3° |
| Physical Description | Solid |
| Stability/Shelf Life | RELATIVELY STABLE IN LIGHT, STABLE @ ROOM TEMP. /HCL/ |
| Kovats Retention Index | 233323552340235624002348.42360.4236623822357.6 |
| Collision Cross Section | 170.35 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]165.25 Ų [M+K]+ [CCS Type: TW163.65 Ų [M+Na]+ [CCS Type: TW |
| Other Experimental Properties | CRYSTALS FROM ABSOLUTE ETHANOL + ETHER. UV MAX (0.1 N H2SO4): 224,285 NM (E AT 1 CM AND 1%= 1,656,355) /HCL/ |
| 沸点 | 419.7°C (rough estimate) |
| 密度 | 0.9917 (rough estimate) |
| 屈折率 | 1.8240 (estimate) |
| 貯蔵条件 | Store at -20°C |
| 外観・状態 | Solid |
| pKa（酸解離定数） | pKa 8.87 (Uncertain) |
| 色 | EtOH (aq) からの結晶 |
| CAS データベース | 129-03-3(CAS DataBase Reference) |
| NISTの化学物質情報 | Cyproheptadine(129-03-3) |
安全性と法規制
| その他の安全情報 | IMAP assessments - Piperidine, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methyl-: Human health tier I assessmentIMAP assessments - Piperidine, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methyl-: Environment tier I assessment |
|---|---|
| FDA 要件 | Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392). |
| Special Reports | Kaliner MAam Fam Physician 45 (3): 1337-42 (1992). Nonsedating antihistamines: pharmacology, clinical efficacy and adverse effects. |
| 保管条件 | Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container. |
| 処分方法 | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Treatment | If vomiting has not occurred spontaneously the patient should be induced to vomit with syrup of ipecac. If the patient is unable to vomit, perform gastric lavage followed by activated charcoal. Isotonic or 1/2 isotonic saline is the lavage of choice. Precautions against aspiration must be taken especially in infants and children. When life threatening CNS signs and symptoms are present, intravenous physostigmine salicylate may be considered. Dosage and frequency of administration are dependent on age, clinical response, and recurrence after response. (See package circulars for physostigmine products.) Saline cathartics, as milk of magnesia, by osmosis draw water into the bowel and, therefore, are valuable for their action in rapid dilution of bowel content. Stimulants should not be used. Vasopressors may be used to treat hypotension. (L1712) |
| 相互作用 | Concurrent use may potentiate the CNS depressant effects of either these medications /alcohol or other CNS depression-producing medications/ or antihistaminesalso, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/Anticholinergic effects may be potentiated when these medications /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistaminespatients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong the intensify the anticholinergic and CNS depressant effects of antihistaminesconcurrent use is not recommended. /Antihistamines/Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/For more Interactions (Complete) data for CYPROHEPTADINE (12 total), please visit the HSDB record page. |
| Hepatotoxicity | Unlike most first generation antihistamines, cyproheptadine has been associated with several instances of clinically apparent liver injury. The few cases that have been described had a time to onset of 1 to 6 weeks and a cholestatic or mixed pattern of liver enzyme elevations. Immunoallergic and autoimmune features were not present and most patients recovered rapidly without residual. Acute liver failure due to cyproheptadine has not been described.Likelihood score: C (probable rare cause of clinically apparent liver injury). |
| 暴露経路 | Well absorbed after oral administration. |
| 毒性の概要 | Cyproheptadine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for Cyproheptadine's ability to stimulate appetite. |
| Signs and Symptoms | Drowsiness, epigastric distress (dysphagia), nausea, vomiting, (it is noted that these side effects are much more common in people with neuromuscular disorders). [Wikipedia] |
| Human Toxicity Excerpts | This compound is thought to inhibit the contractile effect of serotinin on smooth muscles by competing with serotonin for its receptor. 41 Pregnancies were treated with 4 to 16 mg and no teratogenic effects were observed. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)cyproheptadineDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022 |
| Non-Human Toxicity Excerpts | In experiments on chick embryos from various age groups, studies have been made of the effect of a blockader of serotonin receptors: cyproheptadine, and blockader of adrenoreceptors: propranolol, on rhythmic activity of the amnion in vivo after injection of the substances into amniotic fluid. Stimulating effect of propranolol from the 9th to the 19th day of incubation and inhibitory effect of cyproheptadine from the 5th to the 19th day of incubation were revealed. These results indicate the existence of serotonin and noradrenaline in the amniotic fluid of chick embryo. High performance liquid chromatography directly confirmed this conclusion.CYPROHEPTADINE, THE MAIN CONSTITUENT OF THE APPETITE STIMULANT TONIC, MAGNADYN IS A POTENT ANTIHISTAMINE DRUG USED IN THE TREATMENT OF RHINITIS, PRURITUS, URTICARIA, NELSON S SYNDROME & CUSHING S SYNDROME. ITS GENOTOXIC EFFECT WAS INVESTIGATED ON SWISS ALBINO MOUSE BONE MARROW AND PERIPHERAL BLOOD CELLS THROUGH MICRONUCLEUS ANALYSIS. THE TONIC WAS ADMINISTERED ORALLY IN THREE DIFFERENT DOSES VIZ: 0.1 MG/KG, 0.5 MG/KG AND 2.5 MG/KG OF CYPROHEPTADINE IN 0.15 ML QUANTITY. THE THERAPEUTIC DOSE OF 0.5 MG/KG WAS ADMINISTERED DAILY FOR 45 DAYS. ADEQUATE NEGATIVE AND CYCLOPHOSPHAMIDE (50 MG/KG) TREATED POSITIVE CONTROLS WERE MAINTAINED. THE ANIMALS WERE SACRIFICED AT 24, 48 AND 72 HOURS OF ADMINISTRATION TO ASCERTAIN THE DOSE AND TIME-YIELD EFFECT OF THE DRUG. THE DATA WERE SUBJECTED TO MANN-WHITNEY U-TEST. THE EFFECT OF THE DRUG ON MICRONUCLEUS INDUCTION WAS NOT STATISTICALLY SIGNIFICANT IN BOTH THE TESTS. THERE WAS NO SIGNIFICANT CHANGE IN THE P/N RATIO. THE INCIDENCE OF MICRONUCLEUS IN PCE & NCE OF BOTH THE BONE MARROW AND PERIPHERAL BLOOD CELLS OF THE TREATED ANIMALS WERE STATISTICALLY NONSIGNIFICANT COMPARED TO NEGATIVE CONTROL EVEN AFTER LONG TERM ADMINISTRATION. THE ABOVE STUDY CLEARLY SHOWED THAT CYPROHEPTADINE IS NEITHER CLASTOGENIC NOR MITOCLASTIC IN THE PRESENT TEST SYSTEM.The clonal insulin producing cell line RINm5F was evaluated as model for the action of cyproheptadine (CPH)-like diabetogenic compounds in the rat pancreas. Treatment with 10 ug CPH and selected structural analogs under culture conditions produced a progressive loss of cellular insulin which reached 30% of control within 24 hours. Comparison of the activities of the analogs 4-diphenylmethylpiperidine (4-DPMP) and 2-diphenylmethylpiperidine (2-DPMP) to produce cellular insulin depletion showed that 4-DPMP was as active as CPH but 2-DPMP had no activity at the highest concn employed (10 microM). The CPH metabolite desmethyl CPH-epoxide was five times more active than the parent compound in producing loss of insulin in RINm5F cells. These results are consistent with previously published results of CPH actions in vivo. An inhibition of insulin biosynthesis with no loss of preproinsulin mRNA occurred in RINm5F cells treated with CPH or DMCPH-epoxide. This suggests that an effect on transcription may not be the primary action by which CPH and its analogs inhibit insulin synthesis in vivo. |
| Antidote and Emergency Treatment | For treatment of overdose: Since there is no specific antidote for overdose with antihistamines, treatment is symptomatic and supportive with possible utilization of the following: Induction of emesis (syrup of ipecac recommended)however, precaution against aspiration is necessary, especially in infants and children. Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient is unable to vomit within 3 hours of ingestion. Saline cathartics (milk of magnesia) are sometimes used. Vasopressors to treat hypotensionhowever, epinephrine should not be used since it may further lower blood pressure. Oxygen and intravenous fluids. Precaution against use of stimulants (analeptic agents) because they may cause seizures. /Antihistamines/ |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during LactationUnless it is intentionally being used to lower maternal serum prolactin levels, cyproheptadine should be avoided during lactation because it may interfere with lactation, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. The nonsedating antihistamines are preferred alternatives.◉ Effects in Breastfed InfantsRelevant published information on cyproheptadine was not found as of the revision date. In one telephone follow-up study, mothers reported irritability and colicky symptoms 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention and none of the infants were exposed to cyproheptadine.◉ Effects on Lactation and BreastmilkCyproheptadine 16 to 24 mg daily lowers serum prolactin in the treatment of amenorrhea-galactorrhea syndrome because of its antiserotonin activity. Additionally, antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of cyproheptadine has the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. |
| 毒性 | LD50 orl-rat: 295 mg/kg 27ZQAG -,69,72 |
| 税関コード | 29143900 |
| 有害物質データ | 129-03-3(Hazardous Substances Data) |
用途
説明
Cyproheptadine has antianaphylactic activity that is associated with its ability to slow down the release of histamine and other mediators from fat cells.
使用
Antihistaminic; antipruritic.