Nitroarginine (LNNA), an analog of L-arginine, is a competitive inhibitor of nitric oxide synthase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. The Kd value (k(off)/k(on)) of bovine brain cNOS for LNNA was 15 nM. In contrast to the potent and slow onset of LNNA inhibition of brain cNOS, LNNA inhibition of inducible mouse macrophage NOS (iNOS) was weaker (Ki = 4.4 uM) and rapidly reversible. Thus, LNNA was a 300-fold more potent inhibitor of bovine brain cNOS than mouse macrophage iNOS. By inhibiting nitric oxide synthase LNNA causes the selective reduction of blood flow to tumor cells. Despite the potential of LNNA to function as an adjuvant in cancer therapies, its poor solubility and stability have hindered the development of an injectable formulation of LNNA that is suitable for human administration.

Dizocilpine (MK-801) is an antagonist of the N-methyl-D-aspartate (NMDA) receptor in the glutamate category involved with the central nervous system (CNS). The drug displays a variety of physiological actions, many of which involve the CNS, such as anesthetic and anticonvulsant properties. It penetrates readily into CNS and was described as the agent with central sympathomimetic properties. Co-administration of dizocilpine with psychostimulants, such as cocaine, amphetamine and nicotine, has been reported to prevent the development of behavioural sensitization to these drugs as well as associated neuroadaptations in rodents. However, studies with bromocriptine have suggested that co-administration of dizocilpine might merely cause sensitization to become state-dependent. A single injection of MK-801 to rats models both positive and negative symptoms of schizophrenia. Treatment of mice with dizocilpine induced learning impairment.