spiradoline

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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. It has analgesic, diuretic and antitussive effects, and produces subjective effects in animals similar to those of ketocyclazocine and allylnormetazocine. 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. Kappa-agonists have been shown to react negatively with the mu receptor, 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

Spiradoline 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

• Enadoline

References

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

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★リンクテーブル★

リンク元

「オピオイド」

「オピオイド」

　　[★]

英

opioid

同

類麻薬

関

オピオイド受容体

• オピオイド受容体に結合するモルフィン様物質のことを指す。

• 内因性のオピオイドペプチドが発見され、これらは内因性オピオイドペプチドと呼ばれるようになった。

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

Drugs	RECEPTOR TYPES
	μ受容体	δ受容体	κ受容体
morphine	＋＋＋		＋
methadone	＋＋＋
etorphine	＋＋＋	＋＋＋	＋＋＋
levorphanol	＋＋＋
fentanyl	＋＋＋
sufentanil	＋＋＋	＋	＋
DAMGO	＋＋＋
butorphanol	P		＋＋＋
buprenorphine	P		ーー
naloxone	ーーー	ー	ーー
naltrexone	ーーー	ー	ーーー
CTOP	ーーー
diprenorphine	ーーー	ーー	ーーー
β-funaltrexamine	ーーー	ー	＋＋
naloxonazine	ーーー	ー	ー
nalorphine	ーーー		＋
pentazocine	P		＋＋
nalbuphine	ーー		＋＋
naloxone benzoylhydrazone	ーーー	ー	ー
bremazocine	＋＋＋	＋＋	＋＋＋
ethylketocyclazocine	P	＋	＋＋＋
U50,488			＋＋＋
U69,593			＋＋＋
spiradoline	＋		＋＋＋
nor-Binaltorphimine	ー	ー	ーーー
naltrindole	ー	ーーー	ー
DPDPE		＋＋
[[［[D-Ala2,Glu4］deltorphin]]		＋＋
DSLET	＋	＋＋
endogenous Peptides
met-enkephalin	＋＋	＋＋＋
leu-enkephalin	＋＋	＋＋＋
β-endorphin	＋＋＋	＋＋＋
dynorphin A	＋＋		＋＋＋
dynorphin B	＋	＋	＋＋＋
α-neoendorphin	＋	＋	＋＋＋

＋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　　　　－