Tolerance, analgetic effects

The development of tolerance to the analgetic effects of opiates has generally been reported to be retarded by acute Ca + administration, as has dependence development (11-14) In other reports where tolerance development was not affected, it is likely that the dose of Ca + used were insufficient ( 7). 

One might anticipate that the elevated Ca++ would reduce the analgetic effects of La + and EGTA, and the cross-tolerance to these two agents noted in the morphine tolerant state (15, 16) is consistent with such expectations. 

V Clinical - Beecher hais given further support to the ischemic arm pain method for assessing new compounds in healthy volunteers. The same method has been used72 to show that exposure to pain augments the development of tolerance to the analgetic effects of morphine in man. Both cutaneous electrical stimulation and cold pressor effects have been used73 to distinguish aspirin from placebo. 

Clonidine also appears to have significant analgesic properties to which tolerance does not develop. Antinociceptive effects have been demonstrated in many of laboratory tests used to demonstrate analgesia. The effect is centrally mediated. For example, the hot plate assay that demonstrated analgetic properties for clonidine orally failed to do so for other imidazole a-mimetics such as oxymetazoline and tetrahydrazoline, which do not cross the BBB unless administered intracerebrally. 

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