Pharmacology The Dutch Experience of Palfium in the Treatment of Opiate Addicts

[4DQSAR]

Two mangoes in 1979 - prescribing palfium to heroin addicts

 

[damphanduk]

Interesting reading, thanks for sharing!

 

[Allylbenzene]

I wonder how significant TLR4 is regarding opiate habits, tolerance and withdrawals.

Opioid receptor agonists non-stereoselectively activate the TLR4 signaling pathway
— https://doi.org/10.3389/fimmu.2020.01455

Further, representative members of clinically relevant opioids such as morphine, oxycodone, buprenorphine, methadone, pethidine/meperidine, and fentanyl showed efficacy in driving TLR4 signalling in a TLR4 overexpressing cell line.
— https://doi.org/10.1016/j.bbi.2022.02.001

While the role of the immune system, specifically, Toll-like receptor 4 (TLR4) in drug-induced reward is becoming increasingly appreciated...
— https://doi.org/10.1016/j.bbi.2017.08.021

One such side effect is opioid-induced hyperalgesia (OIH), which includes a transition from opioid-induced analgesia to pain enhancement. Evidence in rodents supports the suggestion that OIH may be produced by the action of opioids at Toll-like Receptor 4 (TLR4)
...low dose morphine directly sensitizes human as well as rodent dorsal root ganglion (DRG) neurons, an effect of this opioid analgesic that is antagonized by LPS-RS Ultrapure, a selective TLR4 antagonist.
— http://dx.doi.org/10.1177/17448069241227922

Naltrexone is one of many things which blocks TLR4. Several of the endogenous neurosteroids also block TLR4, eg pregnenolone (OTC).

The researchers focused their attention on the immune receptor Toll-like receptor 4 (TLR4). They administered the drug (+)-Naltrexone which is known to block TLR4, to mice. "Our studies showed a significant reduction in alcohol drinking behavior by mice that had been given (+)-Naltrexone, specifically at night time when the reward for drug-related behavior is usually at its greatest," Mr Jacobsen says. "We concluded that blocking a specific part of the brain's immune system did in fact substantially decrease the motivation of mice to drink alcohol in the evening."

 

[Chaurus]

Two mangoes in 1979 - prescribing palfium to heroin addicts

Just read the introduction. Seen green mangoes for sale in the Albert Cuyp Markt (Amsterdam).

They're still exotic to most of the white Dutch.