Characteristics of Behavioural Stimulant Effect of N‐Cyanomethylmethamphetamine, a Main Product of Smoking Methamphetamine Mixed with Tobacco: Evaluation by Ambulatory Activity in Mice

Abstract

N-cyanomethylmethamphetamine is main product of smoking methamphetamine HCl (CAS code value: 537-46-2, molar mass: 185.70 g/mol) mixed with tobacco, and has a central stimulant action. The aims of this study were to assess in terms of ambulation in mice whether repeated administration of N-cyanomethylmethamphetamine HCl (molar mass: 211.70 g/mol) induced sensitization to its central stimulant effect, and whether there were cross-sensitization from N-cyanomethylmethamphetamine HCl to methamphetamine HCl, and from methamphetamine HCl to N-cyanomethylmethamphetamine HCl. N-cyanomethylmethamphetamine HCl 14.2 and 47.2 mumol/kg subcutaneously dose-dependently accelerated ambulation of mice. Five administrations at 3 day intervals caused sensitization, the activity counts in the fifth administration being approximately 2.6 and 1.6 times, higher respectively, than those in the first administration. Furthermore, the mice repeatedly given 14.2 and 47.2 mumol/kg N-cyanomethylmethamphetamine HCl exhibited cross-sensitization to methamphetamine HCl (10.8 mumol/kg subcutaneously). Whereas 1.4 and 4.7 mumol/kg N-cyanomethylmethamphetamine HCl did not induce significant acceleration of the ambulation throughout the 5 repeated administrations, nor cross-sensitization to methamphetamine HCl. On the other hand, the 5 repeated administrations of methamphetamine HCl (10.8 mumol/kg) also caused sensitization to its ambulation-increasing effect, and the activity count in the fifth administration attained approximately 2.0 times higher than that in the first administration. The mice given methamphetamine HCl demonstrated cross-sensitization to 1.42-14.2 mumol/kg N-cyanomethylmethamphetamine HCl. Haloperidol (CAS code value: 52-86-8, molar mass: 375.88 g/mol; 0.027-0.80 mumol/kg subcutaneously) dose-dependently reduced the ambulation-increasing effects of N-cyanomethylmethamphetamine HCl and methamphetamine HCl in the drug-naive, and N-cyanomethylmethamphetamine HCl- and methamphetamine HCl-sensitized mice. These dose-effect relationships were similar between groups. The present results suggest that N-cyanomethylmethamphetamine HCl has a behavioural stimulant effect almost similar to that of methamphetamine HCl.