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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/07/30 21:36:01」(JST)
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Spiradoline
|
Systematic (IUPAC) name |
2-(3,4-dichlorophenyl)- N-methyl- N-[(5R,7S,8S)- 7-pyrrolidin-1-yl- 1-oxaspiro[4.5]decan-8-yl] acetamide |
Clinical data |
Legal status |
? |
Routes |
N/A |
Identifiers |
CAS number |
87151-85-7 Y |
ATC code |
None |
PubChem |
CID 55652 |
IUPHAR ligand |
1653 |
UNII |
N18ZH0M4NP Y |
ChEMBL |
CHEMBL118865 N |
Chemical data |
Formula |
C22H30Cl2N2O2 |
Mol. mass |
425.392 g/mol |
SMILES
- CN([C@H]1CC[C@@]2(CCCO2)C[C@@H]1N3CCCC3)C(=O)CC4=CC(=C(C=C4)Cl)Cl
|
N (what is this?) (verify) |
Spiradoline (U-62066) is a drug which acts as a highly selective κ-opioid agonist.[1] It has analgesic,[2] diuretic[3] and antitussive effects,[4] and produces subjective effects in animals similar to those of ketocyclazocine and allylnormetazocine.[5] The main effect in humans is sedation, along with analgesic and diuretic effects, but significant side effects such as dysphoria and hallucinations have stopped it from being used clinically.[6] Kappa-agonists have been shown to react negatively with the mu receptor[citation needed], instead of having an assumed synergy since they are both opioid receptors, such as with the mu (μ) receptors and delta (δ) receptors (which both mediate pain-relief, euphoria and overall potency of opioid effects).
Synthesis
The 3-membered cationic intermediate in parenthese is an aziridine, p-TSA is same as TsOH. DBN is acronym for 1,5-Diazabicyclo(4.3.0)non-5-ene.
Spiradoline synthesis: Lester Kaplan.; 1984,
U.S. Patent 4,588,591.
Alternatively, according to scheme two the 2-oxaspiro[4.5]dec-7-ene intermediate can be made by D.A. addition of 2-Methylenebutyrolactone to 1,3-Butadiene followed by reduction and intramolecular ring closure.
2-oxaspiro[4.5]dec-7-ene intermediate: Lester Kaplan.; 1984,
U.S. Patent 4,588,591.
See also
References
- ^ Vonvoigtlander PF, Lewis RA. Analgesic and mechanistic evaluation of spiradoline, a potent kappa opioid. Journal of Pharmacology and Experimental Therapeutics. 1988 Jul;246(1):259-62. PMID 2839665
- ^ Kunihara M, Ohyama M, Nakano M, Hayashi S. Analgesic activity of spiradoline mesylate (U-62,066E), a kappa opioid agonist in mice. Life Sciences. 1989;45(13):1191-8. PMID 2796604
- ^ Yamada K, Imai M, Yoshida S. Mechanism of diuretic action of U-62,066E, a kappa opioid receptor agonist. European Journal of Pharmacology. 1989 Jan 31;160(2):229-37. doi:10.1016/0014-2999(89)90495-0 PMID 2547626
- ^ Kamei J, Tanihara H, Kasuya Y. Antitussive effects of two specific kappa-opioid agonists, U-50,488H and U-62,066E, in rats. European Journal of Pharmacology. 1990 Oct 9;187(2):281-6. PMID 2272363
- ^ Holtzman SG. Further characterization of the discriminative stimulus effects of spiradoline. Pharmacology, Biochemistry and Behaviour. 2000 Jul;66(3):517-22. PMID 10899364
- ^ Wadenberg ML. A review of the properties of spiradoline: a potent and selective kappa-opioid receptor agonist. CNS Drug Reviews. 2003 Summer;9(2):187-98. PMID 12847558
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English Journal
- Role of mu, delta and kappa opioid receptors in ethanol-reinforced operant responding in infant rats.
- Miranda-Morales RS, Spear NE, Nizhnikov ME, Molina JC, Abate P.SourceInstituto de Investigación Médica M. y M. Ferreyra (INIMEC-CONICET), 5016 Córdoba, Argentina.
- Behavioural brain research.Behav Brain Res.2012 Oct 1;234(2):267-77. doi: 10.1016/j.bbr.2012.07.002. Epub 2012 Jul 10.
- We recently observed that naloxone, a non-specific opioid antagonist, attenuated operant responding to ethanol in infant rats. Through the use of an operant conditioning technique, we aimed to analyze the specific participation of mu, delta, and kappa opioid receptors on ethanol reinforcement during
- PMID 22789403
- Early role of the κ opioid receptor in ethanol-induced reinforcement.
- Pautassi RM, Nizhnikov ME, Acevedo MB, Spear NE.SourceInstituto de Investigación Médica M. y M. Ferreyra (INIMEC-CONICET), Córdoba, C.P 5000, Argentina. rpautassi@gmail.com
- Physiology & behavior.Physiol Behav.2012 Mar 20;105(5):1231-41. doi: 10.1016/j.physbeh.2012.01.003. Epub 2012 Jan 11.
- Effects of early ethanol exposure on later ethanol intake emphasize the importance of understanding the neurobiology of ethanol-induced reinforcement early in life. Infant rats exhibit ethanol-induced appetitive conditioning and ethanol-induced locomotor activation, which have been linked in theory
- PMID 22261437
Japanese Journal
- Effects of Spiradoline Mesylate, a Selective κ-Opioid-Receptor Agonist, on the Central Dopamine System with Relation to Mouse Locomotor Activity and Analgesia
- Kunihara Mineo,Ohyama Miwako,Nakano Miyuki
- The Japanese Journal of Pharmacology 62(3), 223-230, 1993
- … Neurochemical and behavioral investigations were made to assess the role of central dopaminergic systems in mouse locomotor activity and analgesia by spiradoline mesylate. … Analgesic activities of the κ-opioid-receptor agonists spiradoline and U-50488H were not altered by haloperidol or L-dopa, whereas morphine analgesia was enhanced by haloperidol but attenuated by L-dopa. …
- NAID 130000840337
Related Pictures
★リンクテーブル★
[★]
- 英
- opioid
- 同
- 類麻薬
- 関
- オピオイド受容体
作用
縮瞳
- モルフィンと多くのμ,κアゴニストは瞳孔の縮小を引き起こす。これは瞳孔を支配する副交感神経の興奮による。μアゴニストを中毒量投与すると縮瞳し、pinpoints pupupilsはpathognomonicである。(GOO.559)
オピオイドとオピオイド類似物質の作用
- GOO.552
+アゴニスト ーアンタゴニスト P partial agonist
各鎮痛薬のオピオイド受容体への作用
- μ受容体 κ受容体
- レミフェンタニル +++ ー
- フェンタニル +++ -
- モルヒネ +++ +
- ペチジン ++ +
- トラマドール + -
- ペンタゾシン ー ++
- ブプレノルフィン P ー
- ナロキソン ー -