Bisabolol as a GABA-A PAM

[polymath]

The terpene compound bisabolol, from some chamomile-like plants, seems to impair motor coordination already at a 10 mg/kg dose. Not sure if anyone thinks this is interesting, but it's another piece of evidence that some plants may contain substances comparable to actual benzodiazepines.

https://www.researchgate.net/publication/318577923_Evidence_for_the_involvement_of_the_GABAergic_but_not_serotonergic_transmission_in_the_anxiolytic-like_effect_of_bisabolol_in_the_mouse_elevated_plus_maze

Bisabolol (α-(−)-bisabolol) is a sesquiterpene which is a part of the essential oil of a variety of plants, but its common source is German chamomile. Several bioactivities including anti-inflammatory, anti-nociceptive, and anti-tumor effects were attributed to bisabolol. However, the neuropharmacological properties of bisabolol have not yet been reported. The present study evaluated behavioral effects of bisabolol using elevated plus maze (EPM), open field test (OFT), and rotarod test. Moreover, this study also examined whether the 5-HT1A and GABAA–benzodiazepine receptor systems are involved in the anxiolytic-like effects of bisabolol. After acute intraperitoneal treatment with bisabolol at the doses of 0.5, 1, 2, 5, and 10 mg/kg, OFT, EPM, and rotarod were utilized for investigating behavioral effects. Flumazenil, a benzodiazepine receptor antagonist, and WAY-100635, a 5-HT1A receptor antagonist, were used to determine the action mechanism in the EPM. Bisabolol especially at the dose of 1 mg/kg was effective in increasing the total number of entries and time spent in the open arms of EPM while number of rearing and grooming in OFT was decreased in comparison to the control. In the rotarod, permanence time was decreased in the mice treated with the high doses of bisabolol. Pretreatment with flumazenil, but not WAY-100635, was able to reverse the effect of bisabolol 1 mg/kg in the EPM, indicating that the anxiolytic-like activity of bisabolol occurs via the GABAergic but not serotonergic transmission. The present study supports the idea that bisabolol may mediate its anxiolytic-like and sedative mechanisms involving GABAA receptors.

 

[sekio]

10 mg/kg injected into rhe body cavity of rats = very weak drug

probably similar to linalool and other terpenes in that they are active in cell culture but you would have to inhale/consume a large amount of essential oil to have it act as a drug

at least thats my opinion as someone who worked with terpenes of all sorts for years

 

[polymath]

Yeah, e.g. the effective antinociceptive dose of racemic methadone for rat is about 0.5-5.0 mg/kg, so you could estimate that bisabolol requires 5 times higher doses. But it's still not a huge amount.

Characterization of the Antinociceptive and Pronociceptive Effects of Methadone in Rats

Background. Recently, it has been appreciated that in addition to their antinociceptive properties, opioid analgesics also can enhance pain sensitivity (opioid-induced hyperalgesia [OIH]). OIH may enhance preexisting pain and contribute to dose escalation, tolerance, and misuse/abuse of opioids...

anesthesiology.pubs.asahq.org

The antinociceptive effect of d,l -methadone was determined as it was related to dose (0.5–5 mg/kg) and sex of the rat, using the high-intensity tail-flick test. At baseline, there were no significant between-sex differences in response (TFL = 2.4 ± 0.09 s [male], 2.2 ± 0.10 s [female]). Responses to a noxious stimulus (TFL) were prolonged after the administration of d,l -methadone, which was indicative of the antinociceptive effect (figs. 1A and B). The highest dose of d,l -methadone (5 mg/kg) produced maximum effect (%MPE = 100% ) in both male and female rats. The antinociceptive effect of d,l -methadone (AUC0–120 min) was related to dose (P < 0.0001; two-way RM ANOVA), but not to sex (fig. 1C). The same was found for maximum %MPE versus dose relation (dose: P < 0.0001; sex: not significant; two-way RM ANOVA). d,l -Methadone had a similar potency in male and female rats (ED50= 1.64 ± 0.15 and 1.75 ± 0.14 mg/kg, respectively).

 

[G_Chem]

Yea and isn’t the typical rat dosage in relations to humans usually fairly high? This is another justification that is used for MDMA neurotoxicity research and the large doses they use. (Although in the case of MDMA human to rat dosages aren’t as different and nearly identical based on blood levels.)

So we could possibly assume that for a human the dosage would be much smaller than 10mg/kg.

-GC

 

[polymath]

For instance, the dose of pentobarbital needed to sedate a rat is something like 50 mg/kg, and for a human it's about 100 mg (total dose, not per kilogram).

 

[llamer]

I don't doubt this at all. D-turbocarane was a component in anethesia for decades after R.E. Shultes identified the tree it is found in by living with Native Amazonia whose hunting involved poison-tipped arrows. Jamaican dogwood must also have GABA-A affinity or something damn similar since it's used by Carribbean fishermen who throw its active parts (the bark? I'm not sure) into stands of fresh water and catch fish stunned from its water-soluble chemicals which are strong enough to steep sizeable bodies of water. A spoonful of the dried herb powder bought from a reputable herb supplier was sufficient for me to feel its effects and typically ensured a night's sleep, and I could compare its effects to that of taking a low dose benzo of sorts. Took a long time to take effect tho, and didn't taste too good.