Safety and Tolerance of Repeated Anesthesia with CI 581 (Ketamine) in Monkeys

The Development of Tolerance to Ketamine in Rats and the Significance of Hepatic Metabolism

“…The work of Douglas & Dagirmanjian (1975) suggested that significant tolerance could be induced in rats by the third successive dose given at four day intervals. Preliminary studies (Livingston & Waterman, 1976) indicated that, in our hands, this dose regime did not produce reliable reductions in sleeping times even after five doses, but a pretreatment regime similar to that used by Bree et al (1967) in monkeys, namely ten daily doses, reliably produced in the rats, as it did in the monkeys, a significant decrease in the sleeping time when compared to control animals, and this 10 daily dose pretreatment schedule resembles the Significance of difference from control at same time point: *P < 0.05; **P < 0.01; ***P < 0.001.…”

“…The possibility that tolerance might develop to repeated doses of the drug was suggested by the work of Bree, Feller & Corssen (1967) in monkeys and clinically by Bjarnsen & Corssen (1967) in patients given ketamine on more than eight occasions and by Bennett & Bullimore (1973) in seven out of ten children given ketamine repeatedly over several weeks . Cronin et al (1972) also recorded the need to increase the dose of ketamine in order to produce adequate sedation in a 6 month old baby after the sixth dose of the drug.…”

Effects of ketamine anaesthesia, stress and repeated bleeding on the haematology of vervet monkeys

“…Its effectiveness and safety as an anaesthetic agent for non-human primates has been reported (Bree, Feller & Corssen, 1967;Bree, 1967). Although haematology values for monkeys given repeated doses have been reported as remaining within the normal range (McCarthy, Chen, Kaump & Ensor, 1965), significant changes in haematological findings have been noted in rhesus monkeys (Loomis, Henrickson & Anderson, 1980).…”

Rapid development of tolerance to sub-anaesthetic dose of ketamine: an oculomotor study in macaque monkeys

“…It is sparsely noted in experimental studies performed on rodents receiving chronic administration of ketamine (Livingston and Waterman 1978) and on primates for anaesthetic purposes (Bree et al 1967;Amemori and Bures 1990;Morgan et al 2009). It is however crucial to be aware of a possible decreased efficacy, since a major characteristic of a pharmacological probe should be to induce reproducible and stable effects, in order to allow the evaluation of new therapeutic agents.…”