Physical-dependence capacity

Many benzomorphan derivatives with morphine-like potencies or better have a low physical dependence capacity (PDC) in monkeys especially potent members, however, such as phenazocine and the /3-isomers (Table 5.2, Nos. 8 and 16) have high to intermediate PDC properties [5, 63, 68]. Unusual results have been reported. for the enantiomorphs of a-(X) (R = Me, R = = Et) the... 

Saelens JK, Granat FR, Sawyer WK (1971) The mouse jumping test a simple screening method to estimate the physical dependence capacity of analgesics. Arch Int Pharmacodyn Ther 190 213-218... 

Primary Physical Dependence capacity is measured on days 11 and 17 when all animals receive an injection of 10 mg/kg of naltrexone or naloxone i.p. in the morning. Signs of withdrawal are recorded during a 30 to 60 min period. Rats are scored for the presence or absence of withdrawal signs (e.g. diarrhea, wet-dog-type shaking) using standardized scoring. 

Mouse jumping as a simple screening method to estimate the physical dependence capacity of opioid agonists has been recommended by Saelens et al. (1971). Mice receive seven i.p. injections over 2 days. The test compound is given at doses increasing in multiples of two until a maximally tolerated dose is reached. Two hours after the last injection the animals receive an i.p. injection of 100 mg/kg naloxone and are placed individually into glass cylinders. The number of jumps is recorded during 10 min. 

In a series of azabicycloalkanes, (17) and its dextro isomer exhibited analgesic activity comparable to meperidine and morphine, respectively.143 The two compounds also exhibited narcotic antagonist activity. (17) Produced slight physical dependence capacity in the Rhesus monkey. 

Inactive, In the III series, all were active - the cyclopropylmethyl analog (IIIc) about five times as active as the methyl (Ilia) analog and without antagonist effect or physical dependence capacity In the monkey. ... 

From a series of morphine derivatives recently synthesized in Hungary, azidomori ne (lla) and azldocodeine (llb) proved to be about 300 times and about 13 times more potent than morj ine, respectively (rat hotplate BTwever, physical dependence capacity (PDC) in mice, rats and... 

As is well known by now, we synthesized a large number of benzomorphans and evaluated several in the clinic. Only two have been subjected to the rigorous examination for physical dependence capacity in Lexington. Neither cycla-zoclne nor pentazocine substitute for morphine in dependent subjects nor do they Induce a morphine-like primary dependence in post-addicts. There is no reason to believe that the other narcotic antagonists would behave differently. Some of the narcotic antagonists which have been studied over the past several years are shown in Chart II. The clinical analgesic activity is recorded in the last column of Table I. 

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