Monkeys morphine withdrawal

Fukase, H. et al., Effects of morphine, naloxone, buprenorphine, butorphanol, haloperidol and imi-pramine on morphine withdrawal signs in cynomolgus monkeys, Psychopharmacology, 116, 396,1994. 

Trilobine Raised pain threshold in mice did not induce or relieve morphine withdrawal symptoms in rats or monkeys and hence is nonaddicting 533... 

Gmerek DE, Dykstra LA, Woods JH (1987) Kappa opioids in rhesus monkeys. III. Dependence associated with chronic administration. J Pharmacol Exp Ther 242 428 136 Katz JL (1986) Effects of clonidine and morphine on opioid withdrawal in rhesus monkeys. Psychopharmacology 88 392-397... 

It also has an antagonist component to its actions, since it inhibits many of the pharmacological effects of morphine and produces withdrawal signs when given to morphine-dependent rats and monkeys. 

The bridged aminotetralin 44 (dezocine, p. 397) is a potent agonist in animals (reports of its agonist actions in the GPI conflict) but has antagonist properties in morphine-dependent monkeys, as shown by its precipitation of a withdrawal syndrome at a potency close to that of nalorphine/100) Dezocine appears to be the only example of an antagonist with a primary amino function and particular aspects of its pharmacological profile may be related to the nitrogen lone-pair orientation as proposed by Belleau (p.464). 

SrV) and feline immunodeficiency vims (FIV), respectively, but studies with these viruses have not provided a clear indication of the influence of opioids on the development of these immunodeficiency diseases. In one study, monkeys maintained on morphine had a slower progression of SIV infection, although temporary withdrawal augmented viral load (Donahoe et al., 1993), but in another, their progression was more rapid (Chuang et al., 1997). Neither acute nor chronic morphine or withdrawal altered FIV infection in cats, but the number of animals was small and the variance in FIV load large (Barr et al., 2003). 

May ct al. demonstrated an extremely signillcani difference between the two i.somcric M-melhyl bcnzoinorphans in which the alkyl in the S position is ii-propyl (R ) and the alkyl in the 9 position is methyl (R l. These have been termed the a and the p isomer and have the groups oriented as indicated. The Isomer with the alkyl cis lo the phenyl possesses analgesic activity (in mice) equal lo that of morphine but has little or no capacity lo. suppress withdrawal symptoms in addicted monkeys. On the other hand, the trans isomer has one of the highest analgesic potencies among the ben/omorphans. but it is quite able 10. suppre.ss morphine... 

In withdrawn morphine-dependent rhesus monkeys, the morphinones exacerbated withdrawal at very low doses. Withdrawal effects persisted even after morphine administration (3 mg/kg, 6 hourly) was resumed [23]. Self-administration and drug discrimination studies in rhesus monkeys were also included in this report. In the drug discrimination assay the codeinones all generalised to codeine. The 4 -bromo- and 4 -methylcinnamoylaminodihydrocodeinones (40b, 40c) were also self-administered but at rates that were below those of codeine [22]. These results confirmed the MOR partial agonist character of the codeinones. 

In morphine-dependent rhesus monkeys, MC-CAM substituted for morphine in withdrawn animals at a dose of 0.8 mg/kg but in non-withdrawn animals the same dose of MC-CAM produced signs of withdrawal slowly over a 3-day period these signs were incompletely suppressed by regular morphine injections [35]. 

The 93-propyl levo Isomer (3c) was considerably more potent subcutaneously than morphine, while the 9oi-propyl levo Isomer (3d) was equipotent with morphine as an analgesic. None of the optical isomers suppressed withdrawal signs in monkeys the 9f5-propyl levo isomer exacerbated the withdrawal syndrome, indicating that it possesses some narcotic antagonist activity.The most active compound (4) of six homobenzomorphans was as potent subcutaneously as morphine (measured by pressure stimuli on mouse tail).115,116 Simplified procedures for the synthesis of the 6,7-benzomor-phan series have been described.117,118 Several 11-hydroxy and 11-alkoxy-2,6-methano-3-benzazocines display as potent analgesic and narcotic antagonist activity as cyclazocine.H ... 

Primary addiction studies in monkeys were carried out with both (-)-cis- and (-)-trans- VIIA. The (-)-cis-compound produced few morphine-Like abstinence signs on abrupt withdrawal after prolonged administration. The (-)-trans-com-pound produced a t5rpical morphine-like abstinence. 

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