Evaluation of the Abuse Potential of Novel Amphetamine Derivatives with Modifications on the Amine (NBNA) and Phenyl (EDA, PMEA, 2-APN) Sites

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.

Treatment of Herpes Simplex Keratitis with IDU and Cryocautery

The effect of IDU and cryocautery in the treatment of Herpes Simplex Keratitis was presented. The cryoapplicator was a model of Krwawlcz probe (2 mm in diameter) which was refrigerated in a mixture of dry ice and methyl alcohol. The applicator was appJied on the lesions 7 seconds each and antibiotics and atropine solutions were instilled. A good result was experienced in the treatment of several cases of dendritic kenititis by freezing the corneal lesions by means of cryoappJicator, which had not been responded to IDU therapy speedy. The deep neovascularization of the cornea in a case of stromal keratitis was disappeared after cryocautery for the treatment of the superficial corneal ulcers.