アルクロニウム
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/01/04 10:01:04」(JST)
[Wiki en表示]
Alcuronium chloride
|
|
Systematic (IUPAC) name |
4,4'-Didemethyl-4,4'-di-propenyltoxiferin-1-dichloride |
Clinical data |
AHFS/Drugs.com |
International Drug Names |
Pregnancy cat. |
? |
Legal status |
? |
Pharmacokinetic data |
Metabolism |
not metabolized |
Excretion |
70–90% unchanged in urine 1.3ml/kg/min t1/2 2–4 hours |
Identifiers |
CAS number |
23214-96-2 N |
ATC code |
M03AA01 |
PubChem |
CID 5311001 |
IUPHAR ligand |
341 |
ChemSpider |
20118193 Y |
UNII |
490DW6501Y N |
ChEBI |
CHEBI:31185 Y |
Chemical data |
Formula |
C44H50N4O2+2 |
Mol. mass |
666.894 g/mol |
SMILES
- [Cl-].[Cl-].OC\C=C6\C[N@+]4(CC=C)CC[C@@]58c%11ccccc%11N7\C=C9\[C@H]1C[C@H]2[C@@]%10(CC[N@@+]2(CC=C)C\C1=C\CO)c3ccccc3N(/C=C(/[C@H]6C[C@H]45)[C@H]78)[C@@H]9%10
|
InChI
-
InChI=1S/C44H50N4O2.2ClH/c1-3-17-47-19-15-43-35-9-5-7-11-37(35)45-26-34-32-24-40-44(16-20-48(40,18-4-2)28-30(32)14-22-50)36-10-6-8-12-38(36)46(42(34)44)25-33(41(43)45)31(23-39(43)47)29(27-47)13-21-49;;/h3-14,25-26,31-32,39-42,49-50H,1-2,15-24,27-28H2;2*1H/q+2;;/p-2/b29-13-,30-14-,33-25-,34-26-;;/t31-,32-,39-,40-,41-,42-,43+,44+,47-,48-;;/m0../s1 Y
Key:CPYGBGOXCJJJGC-GKLGUMFISA-L Y
|
N (what is this?) (verify)
|
Alcuronium is a neuromuscular blocking (NMB) agent, alternatively referred to as a skeletal muscle relaxant. It is a semi-synthetic substance prepared from C-toxiferine I,[1] a bis-quaternary alkaloid obtained from Strychnos toxifera. C-toxiferine I itself has been tested for its pharmacological action and noted to be a very long acting neuromuscular blocking agent[2] For a formal definition of the durations of actions associated with NMB agents, see page for gantacurium. The replacement of both the N-methyl groups with N-allyl moieties yielded N,N-diallyl-bis-nortoxiferine, now recognized as alcuornium (and at one time marketed as the proprietary agent called Alloferin).
Inclusion of the allylic functions presented an enhanced potential area of biotransformation, and thus alcuronium is observed to have a much shorter duration of neuromuscular blocking action than its parent C-toxiferine I.[3] It also has a more rapid onset of action, and is ~1.5 times as potent as tubocurarine.[4] The pharmacological action of alcuronium is readily reversed by neostigmine, and it produced little histamine release.[5] The major disadvantage of alcuronium is that it elicits a vagolytic effect produced by a selective atropoine-like blockade of cardiac muscarinic receptors.[4][6][7]
Effects
- Cardiovascular system: histamine release and blockage of the sympathetic ganglia including adrenal medulla could cause hypotension
- Respiratory: apnea due to phrenic blockage but bronchoconstriction can occur from the histamine release
- Central nervous system: no effect on intraoccular pressure
- Autonomic ganglion blockade can cause decrease in gut motility
Special points
- Duration of action prolonged in states of low potassium, calcium and protein, also in states of high magnesium and acidosis.
- Pharmaceutically incompatible with thiopentone
- Infusion can cause fixed dilated pupils
References
- ^ Foldes FF (1954). Br. J. Anaesth 26: 394.
- ^ Waser PG (1950). Helv. Physiol. Pharmacol. Acta 8: 342.
- ^ Martin-Smith M (1971), In: Ariens EJ (ed.), "Drug Design". Vol. 2. Academic Press. New York and London. pp.453-530.
- ^ a b Speight TM, Avery GS (1972). Drugs 4: 163.
- ^ Thompson MA (1980). Br. J. Hosp Med 23: 153.
- ^ Coleman AJ, Downing JW, Leary WP, Moyes DG, Styles M. (1972). Anaesthesia 27: 415.
- ^ Hughes R, Chapple DJ. (1976). Br. J. Anaesth 48: 59.
- Zahn K, Eckstein N, Tränkle C, Sadée W, Mohr K (2002). "Allosteric modulation of muscarinic receptor signaling: alcuronium-induced conversion of pilocarpine from an agonist into an antagonist". J Pharmacol Exp Ther 301 (2): 720–8. doi:10.1124/jpet.301.2.720. PMID 11961078.
- Maass A, Mohr K (1996). "Opposite effects of alcuronium on agonist and on antagonist binding to muscarinic receptors". Eur J Pharmacol 305 (1-3): 231–4. doi:10.1016/0014-2999(96)00240-3. PMID 8813558.
- Jakubík J, Tucek S (1994). "Protection by alcuronium of muscarinic receptors against chemical inactivation and location of the allosteric binding site for alcuronium". J Neurochem 63 (5): 1932–40. doi:10.1046/j.1471-4159.1994.63051932.x. PMID 7931349.
- Proska J, Tucek S (1994). "Mechanisms of steric and cooperative actions of alcuronium on cardiac muscarinic acetylcholine receptors". Mol Pharmacol 45 (4): 709–17. PMID 8183250.
Skeletal muscle relaxants (M03)
|
|
Peripherally acting
(primarily antinicotinic,
NMJ block) |
Non-depolarizing
|
Curare alkaloids
|
- Alcuronium
- Dimethyltubocurarine
- Tubocurarine
|
|
4° ammonium agents
|
- ultra-short duration: Gantacurium
- short duration: Mivacurium
- Chandonium
- intermediate duration: Atracurium
- Cisatracurium
- Fazadinium
- Rocuronium
- Vecuronium
- long duration: Doxacurium
- Dimethyltubocurarine
- Pancuronium
- Pipecuronium
- Laudexium
- Gallamine
- unsorted: Hexafluronium (Hexafluorenium)
|
|
|
Depolarizing
|
- Choline derivatives: Suxamethonium (Succinylcholine)
- Polyalkylene derivatives: Hexamethonium
|
|
ACh release inhibitors
|
|
|
|
Centrally acting |
Carbamic acid esters
|
- Carisoprodol
- Cyclarbamate
- Difebarbamate
- Febarbamate
- Meprobamate
- Methocarbamol
- Phenprobamate
- Styramate
- Tybamate
|
|
Benzodiazepines
|
- Bentazepam
- Diazepam
- Clonazepam
- Lorazepam
- Nitrazepam
- Tetrazepam
|
|
Anticholinergics (Antimuscarinics)
|
- Cyclobenzaprine
- Orphenadrine
|
|
Other
|
- Baclofen
- Chlormezanone
- Chlorphenesin
- Chlorzoxazone
- Donepezil
- Eperisone
- Fenyramidol
- Flopropione
- Mephenesin
- Mephenoxalone
- Metaxalone
- Pridinol
- Promoxolane
- Quinine
- Thiocolchicoside
- Tizanidine
- Tolperisone
- Trazodone
|
|
|
Directly acting |
|
|
|
anat (h/n, u, t/d, a/p, l)/phys/devp/hist
|
noco (m, s, c)/cong (d)/tumr, sysi/epon, injr
|
|
|
|
|
Cholinergics
|
|
Receptor ligands
|
|
mAChR
|
- Agonists: 77-LH-28-1
- AC-42
- AC-260,584
- Aceclidine
- Acetylcholine
- AF30
- AF150(S)
- AF267B
- AFDX-384
- Alvameline
- AQRA-741
- Arecoline
- Bethanechol
- Butyrylcholine
- Carbachol
- CDD-0034
- CDD-0078
- CDD-0097
- CDD-0098
- CDD-0102
- Cevimeline
- Choline
- cis-Dioxolane
- Ethoxysebacylcholine
- LY-593,039
- L-689,660
- LY-2,033,298
- McNA343
- Methacholine
- Milameline
- Muscarine
- NGX-267
- Ocvimeline
- Oxotremorine
- PD-151,832
- Pilocarpine
- RS86
- Sabcomeline
- SDZ 210-086
- Sebacylcholine
- Suberylcholine
- Talsaclidine
- Tazomeline
- Thiopilocarpine
- Vedaclidine
- VU-0029767
- VU-0090157
- VU-0152099
- VU-0152100
- VU-0238429
- WAY-132,983
- Xanomeline
- YM-796
Antagonists: 3-Quinuclidinyl Benzilate
- 4-DAMP
- Aclidinium Bromide
- Anisodamine
- Anisodine
- Atropine
- Atropine Methonitrate
- Benactyzine
- Benzatropine/Benztropine
- Benzydamine
- BIBN 99
- Biperiden
- Bornaprine
- CAR-226,086
- CAR-301,060
- CAR-302,196
- CAR-302,282
- CAR-302,368
- CAR-302,537
- CAR-302,668
- CS-27349
- Cyclobenzaprine
- Cyclopentolate
- Darifenacin
- DAU-5884
- Dimethindene
- Dexetimide
- DIBD
- Dicyclomine/Dicycloverine
- Ditran
- EA-3167
- EA-3443
- EA-3580
- EA-3834
- Etanautine
- Etybenzatropine/Ethylbenztropine
- Flavoxate
- Himbacine
- HL-031,120
- Ipratropium bromide
- J-104,129
- Hyoscyamine
- Mamba Toxin 3
- Mamba Toxin 7
- Mazaticol
- Mebeverine
- Methoctramine
- Metixene
- N-Ethyl-3-Piperidyl Benzilate
- N-Methyl-3-Piperidyl Benzilate
- Orphenadrine
- Otenzepad
- Oxybutynin
- PBID
- PD-102,807
- PD-0298029
- Phenglutarimide
- Phenyltoloxamine
- Pirenzepine
- Piroheptine
- Procyclidine
- Profenamine
- RU-47,213
- SCH-57,790
- SCH-72,788
- SCH-217,443
- Scopolamine/Hyoscine
- Solifenacin
- Telenzepine
- Tiotropium bromide
- Tolterodine
- Trihexyphenidyl
- Tripitamine
- Tropatepine
- Tropicamide
- WIN-2299
- Xanomeline
- Zamifenacin; Others: 1st Generation Antihistamines (Brompheniramine
- chlorphenamine
- cyproheptadine
- dimenhydrinate
- diphenhydramine
- doxylamine
- mepyramine/pyrilamine
- phenindamine
- pheniramine
- tripelennamine
- triprolidine, etc)
- Tricyclic Antidepressants (Amitriptyline
- doxepin
- trimipramine, etc)
- Tetracyclic Antidepressants (Amoxapine
- maprotiline, etc)
- Typical Antipsychotics (Chlorpromazine
- thioridazine, etc)
- Atypical Antipsychotics (Clozapine
- olanzapine
- quetiapine, etc)
|
|
nAChR
|
- Agonists: 5-HIAA
- A-84,543
- A-366,833
- A-582,941
- A-867,744
- ABT-202
- ABT-418
- ABT-560
- ABT-894
- Acetylcholine
- Altinicline
- Anabasine
- Anatoxin-a
- AR-R17779
- Butinoline
- Butyrylcholine
- Carbachol
- Choline
- Cotinine
- Cytisine
- Decamethonium
- Desformylflustrabromine
- Dianicline
- Dimethylphenylpiperazinium
- Epibatidine
- Epiboxidine
- Ethanol
- Ethoxysebacylcholine
- EVP-4473
- EVP-6124
- Galantamine
- GTS-21
- Ispronicline
- Lobeline
- MEM-63,908/RG-3487
- Nicotine
- NS-1738
- PHA-543,613
- PHA-709,829
- PNU-120,596
- PNU-282,987
- Pozanicline
- Rivanicline
- RJR-2429
- Sazetidine A
- Sebacylcholine
- SIB-1508Y
- SIB-1553A
- SSR-180,711
- Suberylcholine
- Suxamethonium/Succinylcholine
- TC-1698
- TC-1734
- TC-1827
- TC-2216
- TC-5214
- TC-5619
- TC-6683
- Tebanicline
- Tropisetron
- UB-165
- Varenicline
- WAY-317,538
- XY-4083
Antagonists: 18-Methoxycoronaridine
- α-Bungarotoxin
- α-Conotoxin
- Alcuronium
- Amantadine
- Anatruxonium
- Atracurium
- Bupropion
- Chandonium
- Chlorisondamine
- Cisatracurium
- Coclaurine
- Coronaridine
- Dacuronium
- Decamethonium
- Dextromethorphan
- Dextropropoxyphene
- Dextrorphan
- Diadonium
- DHβE
- Dimethyltubocurarine/Metocurine
- Dipyrandium
- Dizocilpine/MK-801
- Doxacurium
- Duador
- Esketamine
- Fazadinium
- Gallamine
- Hexafluronium
- Hexamethonium/Benzohexonium
- Ibogaine
- Isoflurane
- Ketamine
- Kynurenic acid
- Laudexium/Laudolissin
- Levacetylmethadol
- Malouetine
- Mecamylamine
- Memantine
- Methadone (Levomethadone)
- Methorphan/Racemethorphan
- Methyllycaconitine
- Metocurine
- Mivacurium
- Morphanol/Racemorphan
- Neramexane
- Nitrous Oxide
- Pancuronium
- Pempidine
- Pentamine
- Pentolinium
- Phencyclidine
- Pipecuronium
- Radafaxine
- Rapacuronium
- Rocuronium
- Surugatoxin
- Thiocolchicoside
- Toxiferine
- Trimethaphan
- Tropeinium
- Tubocurarine
- Vecuronium
- Xenon
|
|
|
|
Reuptake inhibitors
|
|
Plasmalemmal
|
CHT Inhibitors
|
- Hemicholinium-3/Hemicholine
- Triethylcholine
|
|
|
Vesicular
|
|
|
|
|
Enzyme inhibitors
|
|
Anabolism
|
ChAT inhibitors
|
- 1-(-Benzoylethyl)pyridinium
- 2-(α-Naphthoyl)ethyltrimethylammonium
- 3-Chloro-4-stillbazole
- 4-(1-Naphthylvinyl)pyridine
- Acetylseco hemicholinium-3
- Acryloylcholine
- AF64A
- B115
- BETA
- CM-54,903
- N,N-Dimethylaminoethylacrylate
- N,N-Dimethylaminoethylchloroacetate
|
|
|
Catabolism
|
AChE inhibitors
|
|
|
BChE inhibitors
|
- Cymserine * Many of the acetylcholinesterase inhibitors listed above act as butyrylcholinesterase inhibitors.
|
|
|
|
|
Others
|
|
Precursors
|
- Choline (Lecithin)
- Citicoline
- Cyprodenate
- Dimethylethanolamine
- Glycerophosphocholine
- Meclofenoxate/Centrophenoxine
- Phosphatidylcholine
- Phosphatidylethanolamine
- Phosphorylcholine
- Pirisudanol
|
|
Cofactors
|
- Acetic acid
- Acetylcarnitine
- Acetyl-coA
- Vitamin B5 (Pantethine
- Pantetheine
- Panthenol)
|
|
Others
|
- Acetylcholine releasing agents: α-Latrotoxin
- β-Bungarotoxin; Acetylcholine release inhibitors: Botulinum toxin (Botox); Acetylcholinesterase reactivators: Asoxime
- Obidoxime
- Pralidoxime
|
|
|
|
English Journal
- Semisynthetic analogues of toxiferine I and their pharmacological properties at α7 nAChRs, muscle-type nAChRs, and the allosteric binding site of muscarinic M2 receptors.
- Zlotos DP1, Tränkle C, Holzgrabe U, Gündisch D, Jensen AA.
- Journal of natural products.J Nat Prod.2014 Sep 26;77(9):2006-13. doi: 10.1021/np500259j. Epub 2014 Sep 5.
- A new series of analogues of the calabash curare alkaloid toxiferine I was prepared and pharmacologically evaluated at α7 and muscle-type nAChRs and the allosteric site of muscarinic M2 receptors. The new ligands differ from toxiferine I by the absence of one (2a-c) or two (3a-c) hydroxy groups, sa
- PMID 25192059
- Other drugs acting on nervous system associated with QT-interval prolongation.
- Keller GA1, Ponte ML, Di Girolamo G.
- Current drug safety.Curr Drug Saf.2010 Jan;5(1):105-11.
- Several drugs acting on the nervous system have been implicated in the prolongation of the QT interval. Leaving aside the antidepressant and antipsychotic drugs, some have shown to prolong the QT interval in vivo. These include opioids, particularly methadone, inhalational anesthetics, and some prep
- PMID 20210727
- The impact of orthosteric radioligand depletion on the quantification of allosteric modulator interactions.
- Avlani VA1, McLoughlin DJ, Sexton PM, Christopoulos A.
- The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2008 Jun;325(3):927-34. doi: 10.1124/jpet.108.136978. Epub 2008 Mar 5.
- Radioligand binding assays remain a common method for quantifying the effects of allosteric modulators at G protein-coupled receptors. The allosteric ternary complex model (ATCM) is the simplest model applied to derive estimates of modulator affinity (K(B)) and cooperativity (alpha), which are neces
- PMID 18322151
Japanese Journal
- Unequal effects of cardiopulmonary bypass-induced hypothermia on neuromuscular blockade from constant infusion of alcuronium, d-tubocurarine, pancuronium, and vecuronium
- 非脱分極性筋弛緩薬の作用に及ぼす酸-塩基平衡の影響
- 小野 和身
- 岡山医学会雑誌 98(7-8), 607-612, 1986-08-30
- … The second finding was that the effect of pH changes on the potency of d-Tc and vecuronium was very different from that of metocurine, pancuronium or alcuronium. … In contrast, that of metocurine, pancuronium or alcuronium was antagonized in acidosis and potentiated in alkalosis. …
- NAID 120002306217
- Y-8894の薬理学的研究-3-ラット内包破壊誘発皮質異常脳波に及ぼす影響
- 宇佐 輝人,森本 保人,福田 武美,阿南 惟毅,瀬戸口 通英,丸山 裕
- 日本薬理学雑誌 88(4), 289-297, 1986
- … The effect of Y-8894 on the abnormal electrocorticogram (ECoG) of alcuronium-immobilized rats, induced by destruction of the internal capsule with heat, was compared with that produced by imipramine, amantadine and Ca-hopantenate. …
- NAID 130000759582
Related Links
- Alcuronium is a neuromuscular blocking (NMB) agent, alternatively referred to as a skeletal muscle relaxant. It is a semi-synthetic substance prepared from C- toxiferine I, a bis-quaternary alkaloid obtained from Strychnos toxifera. C- toxiferine I ...
- Alcuroniumchlorid (Alcuronium) ist ein semisynthetisches Derivat des Alkaloids Toxiferin, das den Hauptbestandteil des Calebassen-Curares darstellt, und zählt somit zu den Strychnos-Alkaloiden.
Related Pictures
★リンクテーブル★
[★]
- 英
- alcuronium
- 同
- 塩化アルノルトキシフェリン allnortoxiferin chloride、塩化ジアリルノルトキシフェリン diallylnortoxiferine chloride
- 化
- 塩化アルクロニウム alcuronium chloride