DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, this will not stop me, Only God and death can..........
DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai), INDIA, worlddrugtracker, 29Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.8 Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contributionn, सुकून उतना ही देना प्रभू, जितने से जिंदगी चल जाये।औकात बस इतनी देना,कि औरों का भला हो जाये।...........P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

Thursday 11 February 2016

MELOXICAM

Molecular Structure of 71125-38-7 (Meloxicam)



Meloxicam

351.40, C14H13N3O4S2, MP 255 °C
(8E)-8-[hydroxy-[(5-methyl-1,3-thiazol-2-yl)amino]methylidene]-9-methyl-10,10-dioxo-10$l^{6}-thia-9-azabicyclo[4.4.0]deca-1,3,5-trien-7-one;
4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide;
CAS 133687-22-6; Mobec;Mobic (TN);
2H-1,2-Benzothiazine-3-carboxamide, 4-hydroxy-2-methyl-N-(5-methylthiazolyl)-, 1,1-dioxide;
The IUPAC name of Meloxicam is (3E)-3-[hydroxy-[(5-methyl-1,3-thiazol-2-yl)amino]methylidene]-2-methyl-1,1-dioxo-1λ6,2-benzothiazin-4-one. With the CAS registry number 71125-38-7, it is also named as 2H-1,2-Benzothiazine-3-carboxamide, 4-hydroxy-2-methyl-N-(5-methylthiazolyl)-, 1,1-dioxide.

Uses of Meloxicam: this chemical is a nonsteroidal anti-inflammatory drug with analgesic and fever reducer effects. And it inhibits cyclooxygenase that can be used as an anti-inflammatory. Additionally, it can be used for the treatment of rheumatoid arthritis and osteoarthritis.
In Europe, where the product has been available since the early 1990s, it is also prescribed and licensed for other anti-inflammatory benefits including relief from both acute and chronic pain in dogs and cats. For many years, both injectable and oral (liquid and tablet) formulations of meloxicam have been licensed for use in dogs, and injectable ones for use in cats. In June 2007, a new oral version of Metacam was licensed in Europe for the long-term relief of pain in cats. As of June 2008, Meloxicam is registered for long term use in cats in Australia, New Zealand, and throughout Europe. 'Metacam oral suspension 1.5 is not approved or recommended (according to the manufacture insert) for use in cats in the U.S.
1H NMR DMSOD6


13C NMR DMSOD6

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and fever reducer effects. It is a derivative of oxicam, closely related to piroxicam, and falls in the enolic acid group of NSAIDs.[2] It was developed by Boehringer-Ingelheim. Meloxicam starts to relieve pain about 30–60 minutes after administration.[3]

Mechanism of action

Main article: Non-steroidal anti-inflammatory drug
Meloxicam blocks cyclooxygenase (COX), the enzyme responsible for converting arachidonic acid into prostaglandin H2—the first step in the synthesis of prostaglandins, which are mediators of inflammation. Meloxicam has been shown, especially at its low therapeutic doses, selectively to inhibit COX-2 over COX-1.[1]
Meloxicam concentrations in synovial fluid range from 40% to 50% of those in plasma. The free fraction in synovial fluid is 2.5 times higher than in plasma, due to the lower albumin content in synovial fluid as compared to plasma. The significance of this penetration is unknown,[2] but it may account for the fact that it performs exceptionally well in treatment of arthritis in animal models.[4]

Side effects

Meloxicam use can result in gastrointestinal toxicity and bleeding, headaches, rash, and very dark or black stool (a sign of intestinal bleeding). Like other NSAIDs, its use is associated with an increased risk of cardiovascular events such as heart attack and stroke.[5]It has fewer gastrointestinal side effects than diclofenac,[6] piroxicam,[7] naproxen,[8] and perhaps all other NSAIDs which are not COX-2 selective.[6] Although meloxicam does inhibit thromboxane A, it does not appear to do so at levels that would interfere withplatelet function.
A pooled analysis of randomized, controlled studies of meloxicam therapy of up to 60 days duration found that meloxicam was associated with a statistically significantly lower number of thromboembolic complications than the NSAID diclofenac (0.2% versus 0.8% respectively) but a similar incidence of thromboembolic events to naproxen and piroxicam.[9]

Potential serious cardiovascular side effects

Persons with hypertension, high cholesterol, or diabetes are at risk for cardiovascular side effects. Persons with family history of heart disease, heart attack or stroke must tell their treating physician as the potential for serious cardiovascular side effects is significant.[10][11]

Veterinary use

Meloxicam is also used in the veterinary field, most commonly in dogs and cats, but also sees off-label use in other animals such as cattle and exotics.[12][13] The U.S. Food and Drug Administration sent a Notice of Violation to the manufacturer for its promotional materials which included promotion of the drug for off-label use.[14] In the U.S. the drug is indicated for management of pain and inflammation associated with osteoarthritis in dogs only. In Europe, where the product has been available since the early 1990s,[citation needed] it is also prescribed and licensed for other anti-inflammatory benefits including relief from both acute and chronic pain in dogs. Side effects in animals are similar to those found in humans; the principal side effect is gastrointestinal irritation (vomiting, diarrhea and ulceration). Rarer but important side effects include liver and kidney toxicity.
Since 2003, the oral (liquid) formulations of meloxicam have been licensed in the U.S for use in dogs only,[15] with the January 2005 product insert specifically warning in bold-face type: "Do not use in cats."[16] An injectable formulation for use in dogs was approved by the FDA in November 2003,[17] with a formulation for cats, for surgical use only, approved in October 2004.[18]
In the U.S., per the manufacturer's clinical instructions as of July 2010, injectable meloxicam is indicated in operative use with felines as a single, one-time dose only, with specific and repeated warnings not to administer a second dose.[19] In June 2007, a new oral version of meloxicam was licensed in Europe for the long-term relief of pain in cats. As of June 2008, meloxicam is registered for long term use in cats in Australia, New Zealand, and throughout Europe. A peer-reviewed journal article cites feline overdose of NSAIDs, including meloxicam, as being a cause of severe kidney damage in cats.[20]
The pharmacokinetics of meloxicam have been investigated in koalas (Phascolarctos cinereus).[21]
Meloxicam has been investigated as an alternative to Diclofenac by the RSPB to prevent deaths of vultures.

Preparation of Meloxicam: this chemical can be prepared by Methyl 4-hydroxy-2-methyl-(2H)-1,2-benzothiazine-3-carboxylate-1,1-dioxide and 2-Amino-5-methylthiazole. The yield is 74 %.


References

  1.  Noble, S; Balfour, JA (March 1996). "Meloxicam.". Drugs 51 (3): 424–30; discussion 431–32. doi:10.2165/00003495-199651030-00007. PMID 8882380.
  2.  "Meloxicam official FDA information, side effects, and uses". Drugs.com. March 2010. Retrieved 17 March 2010.
  3.  Auvinet, B; Ziller, R; Appelboom, T; Velicitat, P (November–December 1995). "Comparison of the onset and intensity of action of intramuscular meloxicam and oral meloxicam in patients with acute sciatica.". Clinical Therapeutics 17 (6): 1078–98.doi:10.1016/0149-2918(95)80086-7. PMID 8750399.
  4.  Engelhardt, G; Homma, D; Schlegel, K; Utzmann, R; Schnitzler, C (Oct 1995). "Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance". Inflammation Research 44 (10): 423–433. doi:10.1007/BF01757699. PMID 8564518.
  5.  Stamm O, Latscha U, Janecek P, et al. (January 1976). "Development of a special electrode for continuous subcutaneous pH measurement in the infant scalp". Am. J. Obstet. Gynecol. 124 (2): 193–5. PMID 2012.
  6.  Hawkey, C; Kahan, A; Steinbrü, K; Alegre, C; Baumelou, E; Bégaud, B; Dequeker, J; Isomäki, H; et al. (Sep 1998). "Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients". Rheumatology 37 (9): 937–945(9).doi:10.1093/rheumatology/37.9.937.
  7.  Dequeker, J; Hawkey, C; Kahan, A; Steinbruck, K; Alegre, C; Baumelou, E; Begaud, B; Isomaki, H; et al. (1998). "Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX- inhibiting Therapies (SELECT) trial in osteoarthritis". The British Journal of Rheumatology 37 (9): 946–51.doi:10.1093/rheumatology/37.9.946. PMID 9783758.
  8.  Wojtulewski, JA; Schattenkirchner, M; Barceló, P; Le Loët, X; Bevis, PJR; Bluhmki, E; Distel, M. "A Six-Month Double-Blind Trial to Compare the Efficacy and Safety of Meloxicam 7.5 mg Daily and Naproxen 750 mg Daily in Patients with Rheumatoid Arthritis".Rheumatology. 35, Supplement 1: 22–8. doi:10.1093/rheumatology/35.suppl_1.22.
  9.  Singh, G; Lanes, S; Steinbrü, G; Triadafilopoulos (2004). "Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients". Am J Med 117 (9): 100–6.doi:10.1016/j.amjmed.2004.03.012. PMID 15234645.
  10.  "Medline Plus". Nlm.nih.gov. Retrieved 15 November 2014.
  11.  "Drugs.com". Drugs.com. Retrieved 15 November 2014.
  12.  Off-label use discussed in: Arnold Plotnick MS, DVM, ACVIM, ABVP, Pain Management using Metacam, and Stein, Robert, Perioperative Pain Management Part IV, Looking Beyond Butorphanol, Sep 2006, Veterinary Anesthesia & Analgesia Support Group.
  13.  For off-label use example in rabbits, see Krempels, Dana, Hind Limb Paresis and Paralysis in Rabbits, University of Miami Biology Department.
  14.  US FDA Notice of Violation for off-label use promotion, April 2005.
  15.  "NADA 141-213: New Animal Drug Application Approval (for Metacam (meloxicam) 0.5 mg/mL and 1.5 mg/mL Oral Suspension)" (PDF). US Food and Drug Administration. April 15, 2003. Retrieved 24 July 2010.
  16.  Metacam Client Information Sheet, product description: "Non-steroidal anti-inflammatory drug for oral use in dogs only", and in the "What Is Metacam" section in bold-face type: "Do not use in cats.", January 2005.
  17.  "Metacam 5 mg/mL Solution for Injection" (PDF). Fda.gov. Retrieved 15 November2014.
  18.  "Metacam 5 mg/mL Solution for Injection, Supplemental Approval" (PDF). Fda.gov. October 28, 2004. Retrieved 15 November 2014.
  19.  See the manufacturer's FAQ on its website, and its clinical dosing instructions for cats.
  20.  Merola, Valentina, DVM, DABT, and Dunayer Eric, MS, VMD, DABT, The 10 most common toxicoses in cats, Toxicology Brief, Veterinary Medicine, pp. 340–342, June, 2006.
  21. Kimble, B.; Black, L. A.; Li, K. M.; Valtchev, P.; Gilchrist, S.; Gillett, A.; Higgins, D. P.; Krockenberger, M. B.; Govendir, M. (2013). "Pharmacokinetics of meloxicam in koalas ( ) after intravenous, subcutaneous and oral administration". Journal of Veterinary Pharmacology and Therapeutics 36 (5): 486–493. doi:10.1111/jvp.12038.PMID 23406022.

External links


Meloxicam
Meloxicam2DACS.svg
Systematic (IUPAC) name
4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide.
Clinical data
Trade namesMobic
AHFS/Drugs.commonograph
MedlinePlusa601242
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Routes of
administration		Oral
Pharmacokinetic data
Bioavailability89%[1]
Protein binding99.4%[1]
MetabolismHepatic (CYP2C9 and 3A4-mediated)[1]
Biological half-life20 hours[1]
ExcretionUrine and faeces equally[1]
Identifiers
CAS Number71125-38-7 Yes
ATC codeM01AC06
PubChemCID 5281106
IUPHAR/BPS7220
DrugBankDB00814 Yes
ChemSpider10442740 Yes
UNIIVG2QF83CGL Yes
KEGGD00969 Yes
ChEBICHEBI:6741 
ChEMBLCHEMBL599 Yes
PDB ligand IDMXM (PDBe, RCSB PDB)
Chemical data
FormulaC14H13N3O4S2
Molar mass351.403 g/mol
/////
Cc1cnc(s1)NC(=O)C\3=C(/O)c2ccccc2S(=O)(=O)N/3C
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MIANSERIN

Mianserin3Dan2.gif
Mianserin 2D structure.svg
MIANSERIN
Mianserin (brand names: Depnon (IN), Lantanon (ZA), Lerivon (AR, BE, CZ, PL, RU, SK), Lumin (AU), Norval (UK), Tolvon (AU, HK†, IE†,NZ, SG†), Tolmin (DK); where † indicates discontinued products) is a psychoactive drug of the tetracyclic antidepressant (TeCA) therapeutic family. It is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA) and has antidepressant,anxiolytic (anti-anxiety), hypnotic (sedating), antiemetic (nausea and vomiting-attenuating), orexigenic (appetite-stimulating), andantihistamine effects.
It is not approved for use in the US, but its analogue, mirtazapine, is. Mianserin was the first antidepressant to reach the UK market that was less dangerous than the tricyclic antidepressants in overdose.[3]

Medical uses

When used for the treatment of depression, its efficacy appears comparable to that of amitriptyline, citalopram, clomipramine,dothiepin, doxepin, fluoxetine, flupenthixol, fluvoxamine, imipramine, moclobemide, nortriptyline, paroxetine, and trazodone.[1][4]Mianserin received TGA approval in May 1996.[5]
Similarly to its analogue, mirtazapine, mianserin has been tried as an augmentation strategy in treatment-resistant depression with some success.[6] Mianserin has been tried, similarly to mirtazapine, as an adjunct in schizophrenia and has been found to reduce negative and cognitive symptoms.[7][8][9]
Mianserin has demonstrated efficacy as a monotherapy for the treatment of Parkinson's disease psychosis in an open-label clinical trial.[10]

 

Interactions

CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors (SSRIs), quinidine, ritonavir, etc. would likely raise plasma levels of mianserin and hence could lead to mianserin toxicity. Conversely, CYP2D6 inducers would likely lead to reduced mianserin plasma concentrations and hence potentially diminish the therapeutic effects of mianserin.[1]

Withdrawal

Abrupt or rapid discontinuation of mianserin may provoke a withdrawal, the effects of which may include depression, anxiety, panic attacks,[14] decreased appetite or anorexia,insomnia, diarrhea, nausea and vomiting, and flu-like symptoms, such as allergies or pruritus, among others.

 

Pharmacology

Mianserin is an antagonist/inverse agonist of the H1, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, and α2-adrenergic receptors, and also inhibits thereuptake of norepinephrine.[16][17] As a high affinity H1 receptor inverse agonist, mianserin has strong antihistamine effects (sedation, weight gain, etc.). Contrarily, it has negligible affinity for the mACh receptors, and thus lacks anticholinergic properties. It was recently found to be a weak (Ki = 1.7 μM, EC50 = 0.53 μM) κ-opioid receptor partial agonist.[18]
In addition, mianserin also appears to be a potent antagonist of the neuronal octopamine receptor.[19] What implications this may have on mood are currently unknown, however octopamine has been implicated in the regulation of sleep, appetite and insulin production and therefore may theoretically contribute to the overall side effect profile of mianserin.[20][21]
Blockade of the H1 and α1-adrenergic receptors has sedative effects,[2] and also antagonism of the 5-HT2A and α1-adrenergic receptors inhibits activation of intracellularphospholipase C (PLC), which seems to be a common target for several different classes of antidepressants.[22] By antagonizing the somatodendritic and presynaptic α2-adrenergic receptors which function predominantly as inhibitory autoreceptors and heteroreceptors, mianserin disinhibits the release of norepinephrine, dopamine, serotonin, andacetylcholine in various areas of the brain and body.

Enantioselectivity


 
(S)-mianserin
(S)-(+)-Mianserin is approximately 200–300 times more active than its enantiomer (R)-(−)-mianserin.

 

 

(14bS)-(+)-1,2,3,4,10,14b-Hexahydro-2-methyldibenzo[c,f]pyrazino[1,2-a]azepine (1)
(S)-(+)-1 in the form of solidifying oil; during purification step a small degree of product decomposition was observed; []D 23 = +469.2 (c 1, CHCl3); []D 23 = +436.5 (c 1, EtOH) {[9] []D 23 = +450 (c 0.26, EtOH)}; []D 23 = +428.0 (c 0.5, MeOH) {[5] []D 25 = +469.0 (c 1, MeOH)}.
Enantiomeric purity was determined by HPLC analysis (Chiracel OD-H, hexane:2- propanol = 80:20, 1ml/min, S isomer 5.6min).
IR (CCl4): 3064, 3022, 2939, 2794, 1492, 1446, 1251, 1132 cm–1 ;
1H NMR (500 MHz, CDCl3): δ 2.37-2.42 (m, 4 H), 2.46 (t, J = 10.5 Hz, 1 H), 2.92 (dt, J1 = 2.0 Hz, J2 = 11.0 Hz, 1 H), 3.02 (dd, J1 = 1.5 Hz, J2 = 11.0 Hz, 1 H), 3.25-3.28 (m, 1 H), 3.30 (d, J = 13.0 Hz, 1 H, methylene bridge), 3.42 (td, J1 = 3.0 Hz, J2 = 11.0 Hz, 1 H), 4.14 (dd, J1 = 2.0 Hz, J2 = 10.0 Hz, 1 H,methine), 4.81 (d, J = 13.0 Hz, 1 H, methylene bridge), 6.87 (td, J1 = 1.0 Hz, J2 = 7.5 Hz, 1 H, Ar), 7.00-7.02 (m, 2 H, Ar), 7.05-7.13 (m, 4 H, Ar), 7.16 (td, J1 = 1.5 Hz, J2 = 7.5 Hz, 1 H, Ar);
13C NMR (125 MHz, CDCl3): δ 38.8, 45.6, 51.0, 55.4, 64.6, 66.2, 119.0, 122.3, 126.5, 126.6, 127.0, 127.3, 128.1, 129.5, 137.1, 139.3, 139.8, 148.4.
HRMS (ESI): m/z calcd for C18H21N2 [M+H]+ : 265.1705; found: 265.1712.
(±)-1,2,3,4,10,14b-Hexahydro-2-methyldibenzo[c,f]pyrazino[1,2-a]azepine (1)
The racemate was prepared in the same manner as pure enantiomer; mp = 109.5- 110.5 °C ([10] mp = 111–113 °C). The HPLC analysis (Chiracel OD-H, hexane/2- propanol = 80:20, 1mL/min, R isomer 5.0 min and S isomer 5.6 min)

SYN 1
The title compound has been synthesized by several procedures. Acylation of 2-benzylaniline (I) by chloroacetyl chloride (II) gave chloroacetamide (III). Subsequent cyclization of amide (III) under Vilsmeier conditions furnished the dibenzoazepine (IV). Nucleophilic substitution of the chlorine atom of (IV) by methylamine led to amine (V). The imine function of (V) was reduced with either LiAlH4 or NaBH4 to the diamine (VI), which was further converted into the fused diketopiperazine (VII) upon heating with diethyl oxalate. The amide groups of (VII) were then reduced by means of borane in THF, yielding the target tetracyclic diamine, which was finally isolated as the corresponding hydrochloride salt......US 3534041
SYN 2
In a further procedure, styrene oxide (XV) was condensed with 2-(benzylamino)ethanol (XXVIII) to give amino diol (XXIX). After chlorination of (XXIX) using SOCl2 and DMAP, dichloro derivative (XXX) was condensed with 2-aminobenzyl alcohol (X) yielding piperazine (XXXI). Cyclization of (XXXI) in hot sulfuric acid afforded the tetracyclic compound (XXXII). The N-benzyl group of (XXXII) was then removed by treatment with butyl chloroformate producing carbamate (XXXIII), which was further hydrolyzed and decarboxylated to (XXXIV) under basic conditions. Finally, methylation of the secondary amine (XXXIV) was performed by reductive alkylation with formaldehyde either in the presence of formic acid under Leuckart-Wallach conditions or by catalytic hydrogenation
DE 4305659; EP 0612745
SYN 3
In a different method, reaction of styrene oxide (XV) with methylamine provided amino alcohol (XVI), which was further condensed with ethylene oxide (XVII) to afford amino diol (XVIII). Alternatively, diol (XVIII) was prepared by a more direct procedure by condensation of epoxide (XV) with 2-(methylamino)ethanol (XIX). Chlorination of (XVIII) employing SOCl2 yielded the dichloro derivative (XX), which was subsequently condensed with 2-aminobenzyl alcohol (X) leading to piperazine (XXI). Cyclization of (XXI) to the title compound was accomplished by treatment with hot polyphosphoric acid. Optionally, alcohol (XXI) was converted to chloride (XXII), which was then cyclized in the presence of AlCl3. In a related method, alcohol (XXI) was esterified with AcOH, and the resultant acetate ester (XXIII) was then cyclized in the presence of polyphosphoric acid......US 4217452

The key intermediate (XXI) was also prepared by several related procedures. Chlorination of aminoalcohol (XVI) gave chloro amine (XXIV), which was condensed with 2-aminobenzyl alcohol (X) to afford diamine (XXV). Then, alkylation of diamine (XXV) with dibromoethane (XIII) in hot pyridine gave rise to the target piperazine (XXI). Alternatively, diamine (XXV) was condensed with ethyl chloroacetate or with diethyl oxalate to produce the mono- or dioxopiperazines (XXVII) and (XXVI), respectively, which were then reduced to (XXI) by means of LiAlH4. Cyclization of alcohol (XXI) to the title compound was achieved by treatment with concentrated sulfuric acid

SYN5
FR 2647114
Treatment of alpha-chlorophenylacetyl chloride (VIII) with methylamine provided the corresponding chloro amide (IX), which was subsequently condensed with 2-aminobenzyl alcohol (X) to afford amino alcohol (XI). Cyclization of (XI) in the presence of AlCl3 led to the dibenzoazepine (XII). This was converted to the tetracyclic compound (XIV) by reaction with dibromoethane (XIII) in the presence of Na2CO3. Reduction of the amide carbonyl group of (XIV) by means of LiAlH4 furnished the title compound. In a related strategy, amide (XII) was initially reduced to diamine (VI) by using LiAlH4. Subsequent condensation of (VI) with dibromoethane (XIII) led to the target tetracyclic derivative




OTHER..........

References

  1. Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Sep 29]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  2.  Merck Sharp & Dohme (Australia) Pty Limited. "Tolvon Product Information"(PDF). GuildLink Pty Ltd.
  3.  Walker, R; Whittlesea, C, ed. (2007) [1994]. Clinical Pharmacy and Therapeutics (4th ed.). Edinburgh: Churchill Livingstone Elsevier. ISBN 978-0-7020-4293-5.
  4.  Wakeling A (April 1983). "Efficacy and side effects of mianserin, a tetracyclic antidepressant". Postgrad Med J 59 (690): 229–31. doi:10.1136/pgmj.59.690.229.PMC 2417496. PMID 6346303.
  5.  AlphaPharm. "Lumin Mianserin hydrochloride product information" (PDF). GuildLink Pty Ltd.
  6. Ferreri M, Lavergne F, Berlin I, Payan C, Puech AJ (January 2001). "Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone". Acta Psychiatr Scand 103 (1): 66–72. doi:10.1111/j.1600-0447.2001.00148.x. PMID 11202131.
  7.  Poyurovsky, M; Koren, D; Gonopolsky, I; Schneidman, M; Fuchs, C; Weizman, A; Weizman, R (March 2003). "Effect of the 5-HT2 antagonist mianserin on cognitive dysfunction in chronic schizophrenia patients: an add-on, double-blind placebo-controlled study". European Neuropsychopharmacology 13 (2): 123–128. doi:10.1016/S0924-977X(02)00155-4. PMID 12650957.
  8.  Shiloh, R; Zemishlany, Z; Aizenberg, D; Valevski, A; Bodinger, L; Munitz, H; Weizman, A (March 2002). "Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia". International Clinical Psychopharmacology 17 (2): 59–64.doi:10.1097/00004850-200203000-00003. PMID 11890187.
  9.  Mizuki, Y; Kajimura, N; Imai, T; Suetsugi, M; Kai, S; Kaneyuki, H; Yamada, M (April 1990). "Effects of mianserin on negative symptoms in schizophrenia". International Clinical Psychopharmacology 5 (2): 83–95. doi:10.1097/00004850-199004000-00002.PMID 1696292.
  10.  Ikeguchi, K; Kuroda, A (1995). "Mianserin treatment of patients with psychosis induced by antiparkinsonian drugs". European Archives of Psychiatry and Clinical Neuroscience 244(6): 320–324. doi:10.1007/BF02190411. PMID 7772616.
  11.  "Australian Medicines Handbook". Australian Medicines Handbook Pty Ltd. 2013.
  12.  British National Formulary (BNF) (65th ed.). Pharmaceutical Press. p. 1120.ISBN 978-0857110848.
  13.  Mianserin Hydrochloride. Martindale: The Complete Drug Reference (The Royal Pharmaceutical Society of Great Britain). 5 December 2011. Retrieved 3 November 2013.
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Further reading

External links


Mianserin
Mianserin 2D structure.svg
Mianserin3Dan2.gif
Systematic (IUPAC) name
(±)-2-methyl-1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine
Clinical data
Trade namesBolvidon (discontinued), Tolvon
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Routes of
administration		Oral
Pharmacokinetic data
Bioavailability20–30%[1]
Protein binding95%[1]
MetabolismHepatic (mediated byCYP2D6; most metabolism occurs via aromatic hydroxylation, N-oxidation and N-demethylation)[1]
Biological half-life21–61 hours[2]
ExcretionRenal (4–7%)
Faecal (14–28%)[1]
Identifiers
CAS Number24219-97-4 Yes
ATC codeN06AX03
PubChemCID 4184
IUPHAR/BPS135
DrugBankDB06148 
ChemSpider4040 Yes
UNII250PJI13LM Yes
KEGGD08216 Yes
ChEBICHEBI:51137 
ChEMBLCHEMBL6437 Yes
Chemical data
FormulaC18H20N2
Molar mass264.365



///////////MIANSERIN
c42c(N3C(c1ccccc1C2)CN(C)CC3)cccc4
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