Addiction liability of an isoquinoline analgesic, 1‐(p‐chlorophenethyl)‐2‐methyl‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline

The addictiveness of a new synthetic isoquinolinc. analgesic (I‐K‐1) has been compared with that of morphine, codeine, and D‐propoxyphene in former opiate addicts. Single oral doses of 600 and 1,200 mg. of I‐K‐1 (ten to seventeen times the recommended anolgesic dose) did not induce subjective or objective patterns of morphinelike effects. Intramuscularly and intravenously, I‐K‐1 was identified as an opiate, but it was not possible to give repeated doses of the drug by these routes because of its water insolubility and tissue irritant properties. When I‐K‐1 was substituted for morphine in patients addicted to morphine, it partially prevented development of withdrawal symptoms, but it was only one‐seventh as potent as codeine in this respect. In a direct addiction test that lasted 60 days, using maximally tolerated doses (750 to 1,500 mg. orally daily), I‐K‐1 was disliked by former addicts and when it was discontinued abruptly withdrawal signs were insignificant. It is concluded that I‐K‐1 has substantially less addiction liability than morphine and codeine and even less addictiveness than D‐propoxyphene.