Cocaine SSRIs

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Fourth, as an expert in criminal and civil cases, I have studied the lives of many individuals who—under the influence of psychoactive drugs such as SSRIs, nonselective serotonin reuptake inhibitors (NSRIs), and benzodiazepines—have committed acts of aggression that were wholly alien to their character and antithetical to their prior behavior. It is, of course, well known that the illegal use of stimulant drugs, such as meth-amphetamine and cocaine, can be associated with paranoid reactions and violence. 

The risk of serotonin syndrome may be increased shortly after dosage increases of SSRIs or when drug interactions increase serotonin activity. Concomitant or proximal use of SSRIs, tricyclic antidepressants, or monoamine oxidase inhibitors may cause serotonin syndrome. Further, the addition of certain drugs, such as tryptophan, dextromethorphan, cocaine, or sympathomimetics, to SSRI therapy may increase the risk of developing serotonin syndrome." ... 

Unlike dopamine, 5-HT is released into the general neuronal regions, not just into synapses, and diffuses over a much larger area to activate neuronal 5-HT receptors. 3,4-Methylenedioxy-N-methylamphetamine (MDMA), cocaine, tricyclic antidepressants, and SSRIs all inhibit the removal of 5-HT from neuronal sites. 

An isolated report describes a fatal multiple drug intoxication involving citalopram and cocaine. Animal studies have suggested that SSRIs may potentiate the pro-convulsive effects of cocaine. 

An isolated report describes a fatal multiple drug intoxication involving citalopram and cocaine. It was suggested that SSRIs and cocaine bind to the same receptor site and their concurrent use may have an additive effect through inhibition of serotonin reuptake. The patient also took other drugs including omeprazole, which may have further potentiated the effects of citalopram. ... 

A study in animals suggested that most SSRIs potentiate cocaine-induced convulsions, although sertraline appeared to have no effect on convulsions or lethality. ... 

A Figure 7.2 Basic drugs and classes, the largest subgroup in the acid-base classification scheme. The alkaloids are (or at least once were) derived from plant matter, while nonalkaloids are generally synthetic or semisynthetic. Tropane alkaloids Include cocaine, while tryptamines include mescaline and psilocyn. Caffeine and theophylline are xanthine alkaloids. The selective serotonin reuptake inhibitors (SSRIs) include the second-generation SSRI antidepressants. Prozac (fluoxetine, shown) and Paxil belong to this class. 

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