Table 1: Properties and efficacy of commonly used and upcoming anti-addiction drugs.

NT system

Existing and potential pharmacotherapies

References

Dopamine system

         Normalization of DAergic response

         Alcohol drinking

         Adjuvant treatment for the withdrawal symptoms (WS)

Dopamine receptor partial agonists

         Aripiprazole - D2 receptor partial agonists

         Bromocriptine - WS adjuvant therapy

Brunetti, et al. Kenna, et al. Williams and McBride [147-150].

Dopamine receptor antagonists

         GSK 598809 - D3 receptor antagonists

Te Beek, et al. [151].

GABA system

         Prevents relapse

         Suppresses the WS

GABA receptor modulators

         Gabapentin - GABAB receptor modulator

         Benzodiazepines

 

Karam-Hage and Brower,

Holbrook, et al. [152,153].

5-HT systems

         Decrease in craving and drinking

Selective serotonin uptake inhibitor

         Fluoxetine, Sertraline, Citalopram

         5-HT antagonist ondansetron

Naranjo, et al. Gerra, Babor and Caetano, Dundon, et al. Johnson [154-159].

Brain stress system

         Stress management

         Manage alcohol drinking

         Prevents relapse

         Reduce alcohol drinking

         Adjuvants for the WS

CRF-related targets

         Antalarmin, pexacerfont - CRF receptor antagonists

Hwa, et al. Zorrilla, et al. [160,161].

Non-CRF-related targets

         Prazosin - α1 Adrenergic receptor antagonist

         Naltrexone/β-Funaltrexamine - opioid receptor antagonists

         Norbinaltorphimine - κ opioid receptor antagonist

         Naltrindole - d opioid receptor antagonist

         Nalmefen - and d opioid receptor antagonist

Rasmussen, et al. Volpicelli, et al.

Kranzler, et al. Matsuzawa, et al. Krishnan-Sarin, et al. Froehlich, et al. [162-168].

         Neuropeptide Y receptor agonist

         (Leu31Pro34 NPY)

         Substance P receptor antagonist

         L-760735

Brothers and Wahlestedt, Haddjeri and Blier [169,170].

Glutamate system

      Increases duration of

      Abstinence

      Reduces drinking and facilitates

      Abstinence

      Alcohol dependence and

      Drinking

Glutamate receptor agonists and antagonists

         Acamprosate - N-methyl-D-aspartate (NMDA) receptor partial agonist

         Topiramate - α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist

         3-[(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine (MTEP)mGluR5 antagonist.

 

Kranzler and Gage, Kranzler, et al. Johnson, et al. Johnson, Weiss and Porrino, Blednov and Harris [34,171-176].

Stress management and alcohol craving

         LY-379,268 - mGluR2 and mGluR3 agonist

         (1S,2R,5R,6R)-2-amino-4-oxabicyclo [3.1.0]hexane-2,6-dicarboxylic acid

Zhao and Wu [177].

Antipsychotic activity

Aripiorazole

Wang, et al. [61].