Calcium channel antagonists prevent amphetamine tolerance ? (big post)

[Hellmen]

We know who

(..)Amphetamine tolerance is caused by excess Ca++ influx through the NMDA receptor gated calcium channels on the outer membranes of the dopamine cells bodies in the ventral tegental area, one of two areas in the brain with concentrations of dopamine producing neurons.(..)

So, Can Ca2+ antagonists reverse or prevent tolerance to the amphetamines?

Calcium channel antagonists suppress cross-tolerance to the anxiogenic effects of d-amphetamine and nicotine in the mouse elevated plus maze test.
The purpose of the current experiments was to examine the anxiety-related effects of repeated amphetamine and nicotine administration using the mouse elevated plus maze (EPM). d-amphetamine was administered daily for 8 days (2 mg/kg, i.p.). On the 9th day, mice were challenged with amphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.), and were tested 30 min after this last injection. Additionally, a distinct group of mice was pretreated with nicotine (0.1 mg/kg, s.c., 6 days). These mice were subjected to nicotine (0.1 mg/kg, s.c.) or amphetamine (2 mg/kg, i.p.) challenge on the seventh day to see if full crossover effects developed after the pretreatment of both psychostimulant drugs. Moreover, the L-type voltage-dependent calcium channel antagonists nimodipine (5 and 10 mg/kg, i.p.), flunarizine (5 and 10 mg/kg, i.p.), verapamil (5 and 10 mg/kg, i.p.) and diltiazem (5 and 10 mg/kg, i.p.) were injected prior to each injection of chronic d-amphetamine or nicotine. We observed cross-tolerance to the anxiogenic effects of d-amphetamine and nicotine that was blunted by a pretreatment with calcium channel blockers. Overall our findings imply that similar neural calcium-dependent mechanisms are involved in the anxiety-related responses to chronic amphetamine and nicotine injections. As anxiety seems to be an important factor for the development of psychostimulant dependence, the L-type VDCC antagonists can offer an interesting approach for the pharmacotherapy of addiction, including amphetamine and/or nicotine dependence.

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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http://www.ionchannels.org/showabstract.php?pmid=2076753


Calcium receptor antagonists modify cocaine effects in the central nervous system differently.

L Pani, A Kuzmin, M Diana, G De Montis, GL Gessa, ZL Rossetti
B.B. Brodie Department of Neuroscience, University of Cagliari, Italy.

The effect of different calcium antagonists on cocaine-induced dopamine (DA) release in the striatum, as measured by brain microdialysis in freely moving rats, and on cocaine-induced motor stimulation was studied. While two dihydropyridine calcium antagonists, nimodipine (20 mg/kg) and isradipine (2.5 mg/kg), prevented cocaine-induced DA release and motor stimulation, the diphenylalkylamine-type calcium antagonist flunarizine (20 mg/kg) strongly potentiated both effects of cocaine. Moreover, two calcium antagonists, verapamil (20 mg/kg) and diltiazem (20 mg/kg), were ineffective. The results indicate that various classes of calcium antagonists differ in their interaction with the effects of cocaine in the CNS and suggest that dihydropyridine calcium channel antagonists might be clinically useful for the treatment of cocaine abuse.

 

[Ham-milton]

How do they figure that a drug that strongly potentiates cocaine is going to help prevent abuse???

 

[Coolio]

Diltiazem!? Would this study apply to cocaine as well as amphetamine, or is it amphetamine-specific? Because this would explain why the cartels have been cutting so much cocaine with diltiazem before it even gets to the US.

 

[Hellmen]

Diltiazem!? Would this study apply to cocaine as well as amphetamine, or is it amphetamine-specific? Because this would explain why the cartels have been cutting so much cocaine with diltiazem before it even gets to the US.

The second study only apply to cocaine

 

[LuxEtVeritas]

and it notes diltiazem as ineffective

 

[Coolio]

Ineffective at potentiating dopamine release. However the first study is about eliminating TOLERANCE. I wonder if the second study applies to amphetamine also, and if the first applies to cocaine also?

 

[LuxEtVeritas]

referring to your initial post, a drug dealer wants the indivdual to develop a tolerance and escalating use habit

hence if it potentiated dopamine with C in the least it may cause even greater addicition and more rapid tolerance, but notably it appears to not do so with C