Health Canada Santé Canada STATUS DECISION OF CONTROLLED AND NON-CONTROLLED SUBSTANCE(S) Substance: I- RTI-11 II- RTI-29 III- RTI-31 IV- RTI-32 V- RTI-83 VI- RTI-298 VII- RTI-430 VIII- RTI-436 IX- WIN 35,428 Based on the current information available to the Office of Controlled Substances, it appears that the above substance is: Controlled ☐ Not Controlled X under the schedules of the Controlled Drugs and Substances Act (CDSA) for the following reason(s): The substances are analogues of cocaine and are not included under item 2 of Schedule I to the CDSA. Prepared by: _______________________________________ Date: _______________ Vincent Marleau Verified by: _______________________________________ Date: ________________ Manager, NCED, OCS Approved by: _______________________________________ Date: ________________ DIRECTOR, OFFICE OF CONTROLLED SUBSTANCES This status was requested by: Member of Public 2 Drug Status Report Drug: I- RTI-11 II- RTI-29 III- RTI-31 IV- RTI-32 V- RTI-83 VI- RTI-298 VII- RTI-430 VIII- RTI-436 IX- WIN 35,428 (See Table 1 for chemical information). Pharmacological class / Application: Cocaine analogues International status: US: The substances are not listed specifically in the Schedules to the US Controlled Substances Act and are not mentioned anywhere on the DEA website. United Nations: The substances are not listed on the Yellow List - List of Narcotic Drugs under International Control, the Green List - List of Psychotropic Substances under International Control, nor the Red List - List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances under International Control. Canadian Status: RTI-11, RTI-29, RTI-31, RTI-32, RTI-83, RTI-298, RTI-430, RTI-436, and WIN 35,428 are not listed in the Schedules to the CDSA. The substances are analogues of cocaine, and have primarily been developed for neuroimaging purposes, although they have also been suggested to be useful for smoking cessation purposes1,2. Cocaine is currently listed as sub- item 2(2) “Cocaine (benzoylmethylecgonine)” in Schedule I to the CDSA under the heading “Coca (Erythroxylon), its preparations, derivatives, alkaloids and salts including”. Given that RTI-11, RTI-29, RTI-31, RTI-32, RTI-83, RTI-298, RTI-430, RTI-436, and WIN 35,428 are not synthesized from cocaine and the analogues of cocaine are not captured under the item heading, these substances cannot be included under Item 2 of Schedule I to the CDSA. Recommendation: RTI-11, RTI-29, RTI-31, RTI-32, RTI-83, RTI-298, RTI-430, RTI-436, and WIN 35,428 are not included in the Schedules to the CDSA and are not controlled substances. Date: November 12th, 2013. 1 Phelps, M.E. (2004) PET: Molecular Imaging and its Biological Applications. New York: Springer. 2 Carroll, F.I. (2000) Method of promoting smoking cessation. US patent: US6479509 B1. 3 Table 1: Chemical information Name of Synonyms CAS-RN Chemical Structure Chemical formula substance Methyl 3-(3,4- dichlorophenyl)-8-methyl- RTI-11 8-azabicyclo[3.2.1]octane- 146725-34-0 C16H19Cl2NO2 2-carboxylate; Dichloropane. Methyl 3-(4-aminophenyl)- 8-methyl-8- RTI-29 N/A C H N O azabicyclo[3.2.1]octane-2- 16 22 2 2 carboxylate Methyl 3-(4-chlorophenyl)- 8-methyl-8- RTI-31 130342-80-2 C H ClNO azabicyclo[3.2.1]octane-2- 16 20 2 carboxylate Methyl 8-methyl-3-(p- tolyl)-8- RTI-32 130342-81-3 C H NO azabicyclo[3.2.1]octane-2- 17 23 2 carboxylate Methyl 3-(4-ethylphenyl)-8- methyl-8- RTI-83 155337-52-3 C H NO azabicyclo[3.2.1]octane-2- 18 25 2 carboxylate Methyl 8-methyl-3-(4- (phenylethynyl)phenyl)-8- C H NO RTI-298 N/A 24 25 2 azabicyclo[3.2.1]octane-2- carboxylate Methyl 8-methyl-3-(4-(4- phenylbut-1-yn-1- RTI-430 yl)phenyl)-8- N/A C26H29NO2 azabicyclo[3.2.1]octane-2- carboxylate (E)-Methyl 8-methyl-3-(4- styrylphenyl)-8- C H NO RTI-436 N/A 24 27 2 azabicyclo[3.2.1]octane-2- carboxylate Methyl 3-(4-fluorophenyl)- 8-methyl-8- WIN 35,428 50370-56-4 C H FNO azabicyclo[3.2.1]octane-2- 16 20 2 carboxylate .