STUDIES ON THE PHYSICAL DEPENDENCE OF A NEW CENTRAL ANALGESIC; 1-(m-METHOXYPHENYL)-2-DIMETHYLAMINOMETHYL CYCLOHEXANOL (1) HCL (CG-315)

Abstract

Since earlier studies with nalorphine in humans demonstrated analgesia (1, 2) without producing dependence of the morphine type (1-3), a considerable effort has been made to discover a drug having similar characteristics, but without undesirable psychic effects.Pentazocine was found to be in this category (4-7).<BR> Recently, 1-(m-methoxyphenyl)-2-dimethylaminomethyl cyclohexanol (1) HCl (hereafter referred to as CG-315) was synthesized as a new central analgesic, by Gr&uuml;nenthal Co., Ltd., West Germany. Henmi et al. (8,9) demonstrated that analgesic action of CG-315 is similar to that of dihydrocodeine and also potentiates the response to adrenaline of nictitating membrane and cardiovascular organs in cats. Experiments were carried out to evaluate the physical dependence liability in rats. MATERIALS AND METHODSDonryu S strain white rats of both sexes, weighing from 80 to 100 g were used for all experiments. The rats were kept in individual cages and maintained on a commercial diet (CA-1, Nippon CLEA Co., Ltd., Tokyo). Food and water were not restricted. Animals were usually weighed daily, the mean body weight of control and drug-treated groups being recorded.In the present experiments, the animals were divided (at random) into four groups of twenty. Rats in the first group were given four s.c. injections of morphine daily at 6 hr intervals (6 a.m., noon, 6 p.m. and midnight) for 60-75 consecutive days, unless otherwise noted. The initial dose of morphine was 20 mg/kg/day during the first week (5 mg/kg injected daily x 4; hereafter stated only as the daily dose), 40 mg/kg in the second week, 60 mg/kg in the third week, 80 mg/kg in the 4th week and 100 mg/kg in the 5th week. Animals in this group were maintained at this dose until sacrificed. In the second group of rats given CG-315 (group A), the initial dose of the drug was 20 mg/kg in the first week, 40 mg/kg in the second week, 60 mg/kg in the third week, 90 mg/kg in the 4th week and 120 mg/kg in the 5th week, while in another group (group B) given CG-315, 20 mg/kg was used in the first week, 50 mg/kg in the second week, 80 mg/kg in the third week, 120 mg/kg

Studies on the Physical Dependence Liability of Analgesics

“…On the other hand, CG-315, a newly synthesized analgesic, shows neither the mitochondrial transformation nor fall in body wt. after withdrawal of the drug during chronic administration (2,3).…”

Studies on the Physical Dependence Liability of Analgesics

“…Furthermore, it has been demonstrated that CG-315, a new analgesic, did not produce physical dependence in our experiments (4) and showed no transformation of mitochondria after withdrawal (5), while codeine did cause a moderate transformation (6).…”

“…The time course of the appearance of transformation coincides with that of profound loss in body wt. after withdrawal, the latter being the best index of physical dependence on morphine and related compounds (2)(3)(4).…”