Cocaine’s primary sites of action in the brain include monoamine neurotransmitter transporters for dopamine (DAT), serotonin (SERT) and norepinephrine (NET). DAT, SERT and NET regulate the amount of dopamine, serotonin and norepinephrine available for signal transduction by removing excess monoamine from the synapse back to the presynaptic neuron. Cocaine is able to bind to these transporters and causes a blockade in neurotransmitter reuptake by the presynaptic neuron, thus prolonging neurotransmitter availability in the synaptic cleft. This leads to excessive activation of the postsynaptic neuron, as a consequence of increased binding of the neurotransmitters to their respective receptors, which is manifested as cocaine-induced reward/reinforcement.
The current lack of approved pharmacotherapies in Europe and the US for the treatment of cocaine addiction has prompted the search for novel therapeutic modalities to supplement psychotherapy, a common treatment choice for cocaine dependence which, however, has not been proven to be substantially beneficial for a large number of patients. Effective treatments for addictions must possess the ability to initiate abstinence and prevent subsequent relapse. Celtic Pharma has taken a step forward in this regards and one its conjugate vaccine termed TA-CD is under clinical evaluation. The vaccine, which was generated by covalently attaching succinylnorcocaine to recombinant cholera toxin-B protein adsorbed onto aluminum hydrochloride adjuvant, represents a relapse-prevention therapeutic approach by stimulating the production of cocaine-specific antibodies that bind to cocaine and prevent it from crossing the blood-brain barrier. Blocking cocaine entry into the brain reduces its euphoric and reinforcing effects. The details can be read
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