August 15, 2012

Breakthrough Research: Cure for Morphine Addiction found!!


In a major breakthrough by a group of Australian scientists, a cure has been found for morphine and heroin addiction which will prove a boon for more than 12 million drug addicts worldwide.(1)

Scientists at the University of Adelaide have identified an immune receptor TLR-4 which is responsible for the drug addiction, and found a way to block this receptor without affecting pain relief.


This discovery can have wide implications as it offers the possibility of using Morphine as a pain reliever without worrying about its addictive properties. The use of morphine and other opioids is currently restricted as it can lead to some harmful effects if addicted to it. 

Morphine and other opioids are known to bind to the opioid receptors in the brain, which results in pain relief and also activation of the "Reward Pathway". This "Reward Pathway" is a result of the release of large quantities of Dopamine in the brain which is the root cause for addiction to opioids.


TLR-4 is a toll-like receptor whose role is to identify  foreign bodies,
and thus launch an immune attack against harmful pathogens.
The observation that the opioids also bind to the toll-like receptors TLR-4, eventually led the Hutchinson team to the hypothesis, that TLR-4 may act as an amplifier for award when opioids are bound to it. They performed a series of experiments pertaining to the addictive behaviour in rats, by administering a known drug (called plus naloxone- which is known to block TLR-4), and hence blocking the immune receptors. 

Rats given plus-naloxone before receiving morphine did not exhibit behaviour linked to addiction. Their brains also showed a significantly lower release of dopamine than in rats that only received morphine. Using a heat sensitivity test, the team also showed that the rodents given plus-naloxone still experienced pain relief from the morphine, despite lacking signs of addiction.

The idea that the rewarding effect of opioid drugs is potentially mediated by this receptor "flies in the face of current opinion," says Chris Bailey, a pharmacologist from the University of Bath in the UK. "People for hundreds of years have been trying to come up with an opioid analgesic which isn't rewarding," he says.
These findings are particularly interesting, he says, because it's the first time a mechanism has been identified that separates the pain relief and reward responses to opioid drugs. "It has always been seen that the analgesia and the rewarding aspects go hand in hand," he says.
 The National Institutes on Drug Abuse in U.S is further developing the drug to test in clinical trials. As a result, Clinical trials would soon be underway in the coming 2 years, Dr. Hutchinson said.

If the clinical trials were successful, opioid drugs used to relieve pain could potentially be co-formulated with the additional drugs( TLR-4 Blockers) to limit the chance of addiction.

It would also benefit the addicted patients who are admitted in hospital, and require pain relief. Addicted patients require higher doses of the drug, as they are higly tolerant to the drug, so this combination may help in lowering the doses given to the patients.

August 13, 2012

Public Domain Databases for Medicinal Chemistry


Here's a useful overview of the public-domain medicinal chemistry databases out there. 



BindingDB (quantitative binding data to protein targets).

ChEMBL (wide range of med-chem data, overlaps a bit with PubChem).

PubChem (data from NIH Roadmap screen and many others).

PDB (repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids

Binding MOAD (literature-annotated PDB data).

ChemSpider (26 million compounds from hundreds of data sources).

DrugBank (data on 6700 known drugs).

GRAC and IUPHAR-DB (data on GPCRs, ion channels, and nuclear receptors, and ligands for all of these).

PDBbind (more annotated PDB data).

PDSP Ki (data from UNC's psychoactive drug screening program)

SuperTarget (target-compound interaction database).

Therapeutic Targets Database(database of known and possible drug targets).

ZINC (21 million commercially available compounds, organized by class, downloadable in various formats).




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