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Re: amphetamine sensitization article

Posted by JGalt on November 19, 2001, at 15:51:14

In reply to Re: amphetamine sensitization article Hattree, posted by JohnX2 on November 19, 2001, at 13:09:11

John, did you ever read that web page that I sent you regarding amphetamine tolerance and neurotoxicity?

Here's an interesting excerpt from it:
"Methamphetamine toxicity is inhibited by a variety of drug treatments, including: 1) DA synthesis inhibitor alpha-methyl-para-tyrosine; 2) DA receptor antagonists; 3) NMDA receptor antagonists, e.g., MK-801; 4) DA and serotonergic reuptake inhibitors protecting against DA and serotonin toxicity respectively (195). Even though most studies have found that serotonergic and DA reuptake inhibitors specifically protect these two sites, certain reuptake blockers (such as benztropine) do not (195). On the other hand, mazindol, a non-specific blocker, protects against both DA and serotonergic neurotoxicity. Ali et al. (1994) have further demonstrated in mice that a major factor for neurotoxicity is hyperthermia which is highly correlated with the degree of long-term DA depletion (21). Furthermore, haloperidol, diazepam and MK-801, all of which can reduce methamphetamine-induced hyperthermia, protect rats against DA depletion (4). They also demonstrated that reducing the ambient temperature (4C) reduced neurotoxicity to the same levels found when phenobarbital, diazepam and MK-801 were present to protect the cell. Tolerance to methamphetamine induced by increasing doses also reduces the hyperthermic response and as well protects against neurotoxicity (89, 188).
An important caveat is that not all protective mechanisms act by preventing the hyperthermic effect; the monoamine uptake blockers inhibit neurotoxicity in the absence of inhibition of hyperthermia, e.g., fluoxetine blocks methamphetamine serotonin toxicity without reducing temperature (140). The monoamine protection from neurotoxicity by reuptake inhibition is emphasized by the unexpected discovery that even massive and 24-hour continuous dosing of cocaine, e.g., 100 mg/kg/day, does not result in DA system neurotoxicity (119, 182, 183). Hyperthermia has been well documented to increase amphetamine stereotypy (93, 220). Hyperthermia alone is well known to result in neuronal chromatolysis and has been previously proposed as a significant contributor to amphetamine-induced DA depletion and neuronal damage in clinical as well as experimental animal histopathology (52). Hyperthermia may have been one of the factors resulting in deaths among athletes taking moderate doses of amphetamine in the 1960s and 70s (145). Even in mild hyperthermia, increased body temperature induces a linear decrease in the inhibitory feedback of stimulants on somatodendritic autoreceptors (130). Thus, body temperature changes induced by amphetamine should be considered as one of the contributors to toxicity. "

I've read on this board ppl saying that Prozac+adderal doesn't poop out much...and this mazindol might even be a better idea. What do you think?




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