(+)-Naloxone (dextro-naloxone) is a drug which is the opposite
enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
of the
opioid antagonist drug (−)-
naloxone. Unlike (-)-naloxone, (+)-naloxone has no significant affinity for
opioid receptors, but instead has been discovered to act as a selective
antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
of
Toll-like receptor 4. This receptor is involved in
immune system responses, and activation of TLR4 induces
glial activation and release of inflammatory mediators such as
TNF-α and
Interleukin-1.
Relation with opioids
Both active and inactive enantiomers of various opioid analgesic drugs including
morphine,
meperidine,
fentanyl,
methadone and
buprenorphine, as well as some otherwise inactive metabolites like
morphine-3-glucuronide, have been found to act as agonists of TLR4, and chronic use of these drugs consequently causes constant low-level release of TNF-α and IL-1β as well as other downstream effects. This is thought to be involved in various adverse properties of opioid analgesic drugs, such as loss of efficacy with extended use and the associated development of
tolerance
Tolerance or toleration is the state of tolerating, or putting up with, conditionally.
Economics, business, and politics
* Toleration Party, a historic political party active in Connecticut
* Tolerant Systems, the former name of Veritas Software ...
and
dependence, as well as the development of side effects such as
hyperalgesia and
allodynia, which can cause long-term use of opioid analgesics to not only fail to treat
neuropathic pain, but ultimately exacerbate it.
Applications of (+)-naloxone and related drugs
Several opioid antagonist drugs were found to act as antagonists for TLR4, including naloxone and
naltrexone. However it was found that not only the (-) enantiomers, but also the (+) enantiomers of these drugs acted as TLR4 antagonists (though (+)-
nalmefene
Nalmefene is an opioid antagonist medication used in the management of opioid overdose and alcohol dependence. It is taken by mouth.
Nalmefene is an opiate derivative similar in both structure and activity to the opioid antagonist naltrexone. ...
was inactive). Since (+)-naloxone and (+)-naltrexone lack affinity for opioid receptors, they do not block the effects of opioid analgesic drugs, and so can be used to counteract the TLR4-mediated side effects of opioid agonists without affecting analgesia,
though (+)-naloxone does reduce the reinforcing effects of opioid drugs. (+)-Naloxone was also found to be
neuroprotective,
and both (+)-naloxone and (+)-naltrexone are effective in their own right at treating symptoms of neuropathic pain in animal models.
However (+)-naloxone was also found to reduce the effects of
stimulant
Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
drugs,
suggesting additional actions beyond TLR4 antagonism (possibly as a
sigma receptor antagonist),
that might potentially result in unwanted side effects or drug interactions.
See also
*
Dextromethorphan
*
Eritoran
*
Methylnaltrexone
Methylnaltrexone (MNTX, brand name Relistor), used in form of methylnaltrexone bromide ( INN, USAN, BAN), is a medication that acts as a peripherally acting μ-opioid receptor antagonist that acts to reverse some of the side effects of opioid d ...
References
{{DEFAULTSORT:Naloxone, (+)-
Experimental drugs
Allyl compounds