Structure-activity relationships among some d-N-alkylated amphetamines.
d-N-Alkylated amphetamines were synthesized in a series up to and including d-N-butylamphetamine and potencies of these compounds were compared in (1) rhesus monkeys allowed to respond for intravenous infusions of the drugs, (2) rats allowed to drink a milk solution for 15 minutes each day and (3) isolated, spontaneously beating guinea-pig atria. In the self-administration procedure, d-amphetamine (A), d-N-methylamphetamine (NMA), and d-N-ethylamphetamine (NEA) were self-administered above saline levels at two or more doses by all animals. For these three drugs, maximal response rates were found at similar doses in all animals. However, maximal rates were generally higher in animals maintained on pentobarbital than in animals maintained on cocaine under control conditions. d-N-propylamphetamine (NPA) was self-administered above saline levels by three of four animals at one or more doses. Maximal response rates for NPA were about 1/2 of that of A, NMA and NEA, and the dose-response curve was shifted to the right of these compounds by about 4 times. d-N-butylamphetamine (NBA) maintained responding above saline levels at two doses in only one of three animals. In rats, all of the compounds decreased milk intake in a dose-related manner. A, NMA and NEA were equipotent in disrupting intake, while NPA and NBA were, respectively, 1/4 and 1/6 as potent as the shorter-chain compounds. With the exception of NBA, all compounds increased the rate of beating of the guinea-pig atrium over the range of concentrations tested. In general, for substituents larger than ethyl, potency of d-N-alkylated amphetamines was inversely related to N-alkyl length.
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008892:Milk; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D012646:Self Administration; D013329:Structure-Activity Relationship
C029116:d-N-ethylamphetamine; D008694:Methamphetamine; C029115:d-N-propylamphetamine; C029114:d-N-butylamphetamine; D010424:Pentobarbital; D003042:Cocaine; D003913:Dextroamphetamine