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 - µ opioid receptor antagonists

·         Norbinaltorphimine - κ opioid receptor antagonist

·         Naltrindole - d opioid receptor antagonist

·         Nalmefen - µ 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].