Article is work in progress.

I guess since NMDA receptors have such a role to play in drug tolerance, it isn’t exactly surprising that they seen to attenuate tolerance for alot of other types of drugs as well.

Daily treatment for 7 days with nicotine (0.4 mg/kg s.c.) produced tolerance to the CTA and motor effects. This tolerance was not detectable in rats that had received dizocilpine (NMDA Antagonist) (0.3 mg/kg s.c.) 30 min before each daily injection of nicotine during the period of chronic treatment. The chronic administration of dizocilpine alone did not prevent locomotor effects and CTA when nicotine was administered subsequently. These results suggest that the NMDA receptor may be involved in adaptation to both unconditioned and conditioned behavioural responses to nicotine.

The NMDA antagonist dizocilpine (M K801) attenuates tolerance to nicotine in rats

J Psychopharmacol May 1996 vol. 10 no. 3 214-218 Mohammed Shoaib Ian P. Stolerman Section of Behavioural Pharmacology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK

NMDA receptors mediate the common adaptive processes that are involved in the development, maintenance, and expression of nicotine addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists may prove to be useful in alleviating the symptoms of nicotine abstinence and facilitate tobacco-smoking cessation.

The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review.

Yonsei Med J. 2008 Apr 30;49(2):175-88. Jain R1, Mukherjee K, Balhara YP.

National Drug Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, Pin 110029, India

As expected and seemingly with many other drugs too Memantine as a NDMA antagonist can theoretically successfully prevents the development of tolerance to nicotine.

More work needs to be done on this article, but the hypothetical uses for Nicotine withdrawal or continuous use is promising.

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