ブプレノルフィン 化学特性,用途語,生産方法
効能
鎮痛薬, オピオイド受容体作動薬/拮抗薬
商品名
ノルスパン (ムンディファーマ)
化学的特性
White Solid
使用
Controllled substance (narcotic). Analgesic that demonstrates narcotic agonist-antagonist properties.
定義
ChEBI: A morphinane alkaloid that is 7,8-dihydromorphine 6-O-methyl ether in which positions 6 and 14 are joined by a -CH2CH2- bridge, one of the hydrogens of the N-methyl group is su
stituted by cyclopropyl, and a hydrogen at position 7 is substituted by a 2-hydroxy-3,3-dimethylbutan-2-yl group.
世界保健機関（WHO）
Buprenorphine, an opioid analgesic with both morphine agonist
and antagonist activity, was introduced in 1978. It was originally considered to
possess low dependence potential. However, it has latterly been identified as
causing a socially significant abuse problem in several countries which have
consequently subjected it to control in 1989 under Schedule III of the 1971
Convention of Psychotropic Substances.
(Reference: (UNCPS3) United Nations Convention on Psychotropic Substances (III),
, , 1971)
生物学の機能
Buprenorphine (Temgesic) is a mixed agonist–antagonist
and a derivative of the naturally occurring opioid
thebaine. Buprenorphine is highly lipophilic and is 25 to
50 times more potent than morphine as an analgesic.
The sedation and respiratory depression it causes are
more intense and longer lasting than those produced by
morphine. Its respiratory depressant effects are not
readily reversed by naloxone. It binds to the -receptor
with high affinity and only slowly dissociates from the
receptor, which may explain the lack of naloxone reversal
of respiratory depression.
Buprenorphine has more agonist than antagonist effects
and is often considered a partial agonist rather
than a mixed agonist–antagonist, although it precipitates
withdrawal in opioid-dependent patients. Its pharmacological
effects are similar to those produced by
both morphine and pentazocine. Indications for its use
are similar to those of pentazocine, that is, for moderate
to severe pain. Sublingual preparations are available,
but have a slow onset and erratic absorption.
The abuse potential of buprenorphine is low.While
high doses of the drug are perceived by addicts as being morphinelike, it does reduce the craving for morphine
and for the stimulant cocaine. Thus, buprenorphine is a
potential new therapy for the treatment of addiction to
both classes of drugs.
Drug interactions and contraindications are similar
to those described for pentazocine and morphine.
一般的な説明
Buprenorphine is a semisynthetic, highly lipophilic opiate derivedfrom thebaine. Pharmacologically, it is classified as amixed μ-agonist/antagonist (a partial agonist) and a weak κ-antagonist. It has a high affinity for the μ-receptors(1,000 times greater than morphine) and a slow dissociationrate leading to its long duration of action (6–8 hours). Atrecommended doses, it acts as an agonist at the μ-receptorwith approximately 0.3 mg IV equianalgesic to 10 mg of IVmorphine. One study in humans found that buprenorphine displaysa ceiling effect to the respiratory depression, but not theanalgesic effect over a dose range of 0.05 to 0.6 mg.In practice,this makes buprenorphine a safer opiate (when usedalone) than pure μ-agonists. Relatively few deaths frombuprenorphine overdose (when used alone) have been reported.113 The tight binding of the drug to the receptor also hasled to mixed reports on the effectiveness of using naloxone toreverse the respiratory depression. In animal studies, normaldoses of the pure antagonist naloxone were unable to removebuprenorphine from the receptor site and precipitate withdrawal.In a human study designed to precipitate withdrawalfrom buprenorphine, a naloxone dose (mean=35 mg) 100times the dose usually needed to precipitate withdrawal inmethadone-dependent subjects was used. For comparison, approximately0.3 mg, 4 mg, 4 mg, and 10 mg of naloxonewould be required to precipitate withdrawal from heroin, butorphanol,nalbuphine, or pentazocine respectively.
接触アレルゲン
This semisynthetic opioid analgesic drug is derived fromwith transdermal systems (TDS). In case of localized or
generalized allergic contact dermatitis due to buprenorphine
in TDS, TDS containing fentanyl can be safely used
thebaine. It can be used parenterally, orally, and topically
薬理学
Buprenorphine is the only partial agonist in common use. It binds to the
MOP receptor and dissociates from it very slowly. Consequently, although
significant respiratory depression is less likely compared with morphine, it
may be more difficult to reverse. It has poor oral bioavailability, and
parenteral, sublingual or transdermal formulations are used. In addition to partial agonism at the MOP receptor, it is also a partial agonist at the NOP receptor and an antagonist at the KOP receptor. This may contribute to some
of its analgesic effects. Increasingly it is also used instead of methadone for
the management of opioid abuse (usually in relatively large doses up to
24 mg day?1).
ブプレノルフィン 上流と下流の製品情報
原材料
準備製品