NeuroSearch A/S, of Glostrup, Denmark, has received approval to carry out a Phase I clinical trial in the U.K. of NS2359 for the treatment of cocaine addiction.

The trial will be financed by the U.S. National Institute of Drug Abuse (NIDA), based in Baltimore, which singled out the NeuroSearch compound because, in animal testing, it blocked self-injection of cocaine at low doses without affecting behavior.

While NIDA has agreed to finance the development of NS2359, NeuroSearch CEO Jorgen Buss Lassen told BioWorld International the company retains all commercial rights to the compound. If development is successful, NIDA will help the Danish company find U.S. pharmaceutical partners.

“NIDA did the preclinical work in the U.S., but we decided to go ahead with Phase I in the U.K. because we could perform it earlier,“ said Buss Lassen. “NIDA plans to conduct Phase II in the U.S. It will finance that and then help us to find a pharmaceutical partner. We won't do any further trials in Europe until we have the U.S. results.“

Addicts who try to stop taking cocaine after prolonged use suffer a fall in activity of the neurotransmitter dopamine in the reward center of the brain. This is experienced by patients as strikingly diminished pleasure or loss of interest in most activities. These effects lead to cocaine craving and drug-seeking behavior.

NeuroSearch and NIDA believe that by inducing a stable, moderate enhancement of dopaminergic activity over a prolonged period, NS2359 may provide an effective therapy for addiction.

“NIDA achieved unique results using our compound in animal models,“ said Buss Lassen. In the model, animals press a lever to self-administer cocaine and thus develop an addiction. “NIDA selected our drug because at low doses it blocked self-injection without affecting behavior. This effect had not been seen before in any other compound.“

Buss Lassen said the mechanism of action is not fully known. “Cocaine produces a huge increase in dopamine production. After using it for a long time there is a significant reduction in dopamine function, causing craving. NS2359 initiates a low-level onset of dopamine production that does not go beyond normal levels. In addition, the effect lasts for a long time.“

One million to 2 million people in the U.S. are estimated to be cocaine-dependent. Although Buss Lassen recognizes NS2359 could be commercially significant for NeuroSearch, he said, “Only time will tell if this compound is as active in addicts as in animals.“ *