Noribogaine has been determined to act as a
biased agonist of the
κ-opioid receptor (KOR).[13] It activates the
G protein (GDP-GTP exchange) signaling pathway with 75% the efficacy of
dynorphin A (
EC50 = 9 μM), but it is only 12% as efficacious at activating the
β-arrestin pathway.[13] Moreover, due to its very low efficacy on the β-arrestin pathway, noribogaine blocked dynorphin A activation of the pathway (
IC50 = 1 μM) and hence functioned as an
antagonist of it.[13]
The β-arrestin pathway is thought to be responsible for the
dysphoric and
aversive effects of KOR activation,[14] and its lack of activation by noribogaine may be the reason for the lack of dysphoric effects of the drug.[13] This biased agonist/antagonist action of noribogaine at the KOR is unique to it relative to other
iboga alkaloids and related compounds such as
ibogaine and
18-methoxycoronaridine (18-MC).[13] Moreover, it has been hypothesized that it may give noribogaine unique properties such that it may have the
analgesic and
antiaddictive effects of KOR agonists without the
anxiogenic,
dysphoric, or
anhedonic effects that are typical of them.[13]
^Mash DC, Ameer B, Prou D, Howes JF, Maillet EL (2016). "Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents". J. Psychopharmacol. (Oxford). 30 (7): 688–97.
doi:
10.1177/0269881116641331.
PMID27044509.
S2CID40776971.
^Baumann MH, Pablo J, Ali SF, Rothman RB, Mash DC (2001). "Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine". The Alkaloids: Chemistry and Biology. 56: 79–113.
doi:
10.1016/S0099-9598(01)56009-5.
PMID11705118.
Noribogaine has been determined to act as a
biased agonist of the
κ-opioid receptor (KOR).[13] It activates the
G protein (GDP-GTP exchange) signaling pathway with 75% the efficacy of
dynorphin A (
EC50 = 9 μM), but it is only 12% as efficacious at activating the
β-arrestin pathway.[13] Moreover, due to its very low efficacy on the β-arrestin pathway, noribogaine blocked dynorphin A activation of the pathway (
IC50 = 1 μM) and hence functioned as an
antagonist of it.[13]
The β-arrestin pathway is thought to be responsible for the
dysphoric and
aversive effects of KOR activation,[14] and its lack of activation by noribogaine may be the reason for the lack of dysphoric effects of the drug.[13] This biased agonist/antagonist action of noribogaine at the KOR is unique to it relative to other
iboga alkaloids and related compounds such as
ibogaine and
18-methoxycoronaridine (18-MC).[13] Moreover, it has been hypothesized that it may give noribogaine unique properties such that it may have the
analgesic and
antiaddictive effects of KOR agonists without the
anxiogenic,
dysphoric, or
anhedonic effects that are typical of them.[13]
^Mash DC, Ameer B, Prou D, Howes JF, Maillet EL (2016). "Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents". J. Psychopharmacol. (Oxford). 30 (7): 688–97.
doi:
10.1177/0269881116641331.
PMID27044509.
S2CID40776971.
^Baumann MH, Pablo J, Ali SF, Rothman RB, Mash DC (2001). "Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine". The Alkaloids: Chemistry and Biology. 56: 79–113.
doi:
10.1016/S0099-9598(01)56009-5.
PMID11705118.