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| Systematic (IUPAC) name | |
|---|---|
| (±)-5-(4-chlorophenyl)-3,5-dihydro-2H-imidazo[2,1-a]isoindol-5-ol | |
| Clinical data | |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Pregnancy cat. | ? |
| Legal status | Schedule IV (US) Schedule IV (International) |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 93% |
| Metabolism | Hepatic |
| Half-life | 10-13 hours |
| Excretion | Renal |
| Identifiers | |
| CAS number | 22232-71-9 Y |
| ATC code | A08AA05 |
| PubChem | CID 4020 |
| DrugBank | DB00579 |
| ChemSpider | 3880 Y |
| UNII | C56709M5NH Y |
| KEGG | D00367 Y |
| ChEMBL | CHEMBL781 Y |
| Chemical data | |
| Formula | C16H13ClN2O |
| Mol. mass | 284.74 g/mol |
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| Y (what is this?) (verify) |
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Mazindol (Mazanor, Sanorex) is a stimulant drug of the tetracyclic chemical class which is used as an anorectic.[1] It was developed by Sandoz-Wander in the 1960s[2]
Contents
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Indications
Mazindol is used in short-term (i.e., a few weeks) treatment of exogenous obesity, in combination with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of 30 kg of body weight per height in meters squared (kg/m2), or in patients with a body mass index of 27 kg/m2 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia.
Pharmacology
Mazindol is a sympathomimetic amine, which is similar to amphetamine. It stimulates the central nervous system, which increases heart rate and blood pressure, and decreases appetite. Sympathomimetic anoretics (appetite suppressants) are used in the short-term treatment of obesity. Their appetite-reducing effect tends to decrease after a few weeks of treatment. Because of this, these medicines are useful only during the first few weeks of a weight-loss program.
Although the mechanism of action of the sympathomimetics in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Like other sympathomimetic appetite suppressants, mazindol is thought to act as a reuptake inhibitor of norepinephrine. In addition, it inhibits dopamine and serotonin reuptake. The recommended dosage is 2 mg per day for 90 days in patients with 40 kg of overweight or less, 4 mg a day in patients with more of 50 kg of overweight, separated in two ingestion with a 12 hour window between each 2 mg dose.
Overdose
Symptoms of a mazindol overdose include: restlessness, tremor, rapid breathing, confusion, hallucinations, panic, aggressiveness, nausea, vomiting, diarrhea, an irregular heartbeat, and seizures.
Synthesis
[Satendra Singh, 2000, Chem. Rev., 925-1024]
Analogs[3]
From considering the attached QSAR table we can make the apparent observations:
- Desoxylation of the tertiary alcohol in mazindol improves DAT and SERT binding. The compound now behaves as a functional SNDRI instead of predominantly a noradrenaline reuptake inhibitor.
- Removal of the p-chloro atom in mazindol means that the compound now only behaves as a noradrenaline reuptake inhibitor.
- Changing the size of the imidazoline type ring system in mazindol to the corresponding six-membered homolog increases potency of the resultant compound at the DAT by approximately ten-fold.
| n | R | R' | R" | hSERT | hNET | hDAT |
|---|---|---|---|---|---|---|
| 1 | Cl | H | OH | 94 | 4.9 | 43 |
| 1 | Cl | H | H | 15 | 6.9 | 6.0 |
| 1 | H | H | OH | 2140 | 2.8 | 730 |
| 1 | -C4H4- | OH | 1.8 | 4.5 | 66 | |
| 2 | Cl | H | OH | 53 | 4.9 | 3.7 |
| 2 | OH | H | OH | 60 | 1.9 | 59.0 |
| 2 | OMe | H | OH | 94 | 4.1 | 30.4 |
| 2 | -OCH2O- | OH | 83 | 0.62 | 2.21 | |
To make the six membered (so-called homomazindol) analog, one can simply substitute 1,2-diaminoethane with 1,3-diaminopropane. Importantly, another procedure was also published.
Given the data in the above table, one might also be interested in making the desoxy-mazindol analog. The synthesis for this is facile. Although "mazindane" is relatively stable in air, it is readily oxidized to mazindol upon contact with monoamine oxidaze enzymes present at the DAT.
See also: SNDRI for context.
See also
- Ciclazindol
References
- ^ Carruba, Michele O.; Zambotti, Fernanda; Vicentini, Lucia; Picotti, Giovanni B.; Mantegazza, Paolo (1978). "Pharmacology and biochemical profile of a new anorectic drug: mazindol". Cent. Mech. Anorectic Drugs: 145–64.
- ^ US Patent 3597445 - 1H-Isoindole Intermediates
- ^ Houlihan, WJ; Ahmad, UF; Koletar, J; Kelly, L; Brand, L; Kopajtic, TA (2002). "Benzo- and cyclohexanomazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter". Journal of Medicinal Chemistry 45 (19): 4110–8. doi:10.1021/jm010301z. PMID 12213054. editHoulihan, WJ; Kelly, L; Pankuch, J; Koletar, J; Brand, L; Janowsky, A; Kopajtic, TA (2002). "Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter". Journal of Medicinal Chemistry 45 (19): 4097–109. doi:10.1021/jm010302r. PMID 12213053. edit
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- Lee S, Kim J, In S, Choi H, Oh SM, Jang CG, Chung KH.SourceCollege of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu, 704-701, Republic of Korea.
- Analytical and bioanalytical chemistry.Anal Bioanal Chem.2012 May;403(5):1385-94. Epub 2012 Mar 30.
- Owing to the tight control of methamphetamine, it is presumed that phentermine, an amphetamine-type anorectic, has recently been considered a supplement for methamphetamine abusers in Korea. In addition, the abuse of other anorectics obtained by inappropriate means has become a social issue. Hair is
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- Inocente C, Arnulf I, Bastuji H, Thibault-Stoll A, Raoux A, Reimão R, Lin JS, Franco P.SourceIntegrative Physiology of Brain Arousal System, CRNL, INSERM-U1028, CNRS UMR5292, University Lyon1, Lyon, France.
- Clinical neuropharmacology.Clin Neuropharmacol.2012 Mar-Apr;35(2):55-60.
- OBJECTIVE: Narcolepsy is a rare disabling sleep disorder characterized by excessive daytime sleepiness and cataplexy (sudden loss of muscle tone). Drugs such as pitolisant, which block histamine H3 autoreceptors, constitute a newly identified class of stimulants because they increase brain histamine
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Japanese Journal
- Pharmacology in Health Foods : Merits and Demerits of Food With Health Claims for the Prevention of Metabolic Syndrome
- SAKANE Naoki
- Journal of pharmacological sciences 115(4), 476-480, 2011-04-20
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Related Links
- Mazindol is used in short-term (i.e., a few weeks) treatment of exogenous obesity, in combination with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of 30 kg of ...
Related Pictures
★リンクテーブル★
| リンク元 | 「ドパミン」「マジンドール」 |
「ドパミン」
- 英
- dopamine DA DOA 3,4-dihydroxyphenethylamine
- 同
- ドーパミン
- 化
- 塩酸ドパミン, dopamine hydrochloride, ドパミン塩酸塩
- 商
- イノバン、イブタント、カコージンD、カコージン、カタボン、ガバンス、クリトパン、ツルドパミ、ドパラルミン、ドミニン、トロンジン、プレドパ、マートバーン、ヤエリスタ
- 関
- ドパミン受容体、カテコラミン。強心剤
概念
- カテコラミンの一つ
生合成
視床下部-下垂体系
- 視床下部弓状核や脳室周辺の隆起漏斗系ドパミンニューロンで産生される。
- 下垂体のD2受容体を介してホルモン分泌の調節を受けている。 → e.g. プロラクチン放出抑制ホルモン(PIF)
ドパミン受容体
- 低用量での血管拡張はこの受容体を介して起こる (GOO.249)
- 中枢神経系に存在
神経伝達物質の薬理 (GOO.324)
| 神経伝達物質 | トランスポーター阻害薬 | 受容体のサブタイプ | 選択的作動薬 | 選択的阻害薬 | 受容体と共役する分子 |
| ドパミン | cocaine mazindol nomifensine |
D1 | Gs | ||
| D2 | bromocriptine | sulpiride domperidone |
Gi | ||
| D3 | 7-OH-DPAT | ||||
| D4 | |||||
| D5 | Gs |
薬理学
- 低濃度
- D1受容体に作用して血管拡張→腎血流量↑→GFP↑→Na排出↑→利尿
- やや高濃度
- β1受容体に作用→心拍出量↑・心収縮力↑(頻脈はない)・収縮期圧↑・拡張期圧不変
- アドレナリン低用量投与と同じ？
- 高濃度
- α1受容体に作用→血管平滑筋収縮(→収縮期圧↑、拡張期圧↑？？？)
- アドレナリン高用量投与と同じ？
ran]]
(PT.218)
- 中脳に細胞体を持つものが多く、黒質から線条体に至る黒質線条体系と黒質や腹側被蓋野から報酬系の神経核、辺縁系、前頭葉に至る中脳皮質系がある。視床下部やその周辺にもドーパミン作動性線維の細胞体とその終末があり、隆起漏斗系、隆起下垂体系、不確帯視床下部系、脳室周囲系を形成する。黒質線条体系の変性はパーキンソン病をもたらす。ドーパミン誘導体には幻覚剤となるものがある。ドーパミンの分泌増大や脳のD2受容体の増加は精神分裂病（統合失調症）の発病に関与している可能性がある。モルヒネはドーパミンの分泌を促進する。コカインは輸送体によるドーパミンの取り込みを阻害し作用の持続時間を延長する。一部の覚醒剤中毒はドーパミン輸送体の抑制による。
ホルモンの調節
- プロラクチンは視床下部でドパミンの産生を促進 ← プロラクチン抑制因子として作用
- ドパミンは視床下部でGnRHの分泌を抑制 → 卵巣機能の抑制
- ドパミンは下垂体前葉？でD受容体に作用してプロラクチンを抑制 ← 抗精神病薬(D2受容体をブロックする)を使うと高プロラクチン血症となる。
循環不全治療薬として
- イノバン
- 下記のような急性循環不全(心原性ショック、出血性ショック)