Selective serotonin reuptake inhibitors amphetamines

VMATs are not inhibited by drugs such as cocaine, tricyclic antidqnessants and selective serotonin reuptake inhibitors that affect plasma membrane monoamine transport. Amphetamines have relatively selective effects on monoaminergic cells due to selective uptake by plasma membrane monoamine transporters, but their effect appears to be mediated by their ability as weak bases to reduce ApH, the driving force for vesicular monoamine transport that leads to efflux of the vesicular contents into the cytoplasm. 

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). 

Antidepressants selective serotonin reuptake inhibitors, tricyclic antidepressants Antihypertensives felodipine Antibiotics quinolones, isoniazid Bronchodilators albuterol, theophylline Corticosteroids prednisone Dopa agonists levodopa Herbals ma huang, ginseng, ephedra Nonsteroidal anti-inflammatory drugs ibuprofen Stimulants amphetamines, methylphenidate, caffeine, cocaine Sympathomimetics pseudoephedrine Thyroid hormones levothyroxine Toxicity anticholinergics, antihistamines, digoxin Withdrawal alcohol, sedatives... 

The majority of patients need medication for the two main symptoms. Drugs with CNS-stimulating effects, mostly of the amphetamine type, are used to alleviate excessive sleepiness and sleep attacks. The resulting increased level of vigilance also decreases or abolishes cataplexy in a number of patients. If this is not achieved, tricyclic antidepressants, in the hrst instance, and selective serotonin (5-hydroxytryptamine 5-HT) reuptake inhibitors, in the second instance, can be used to control cataplexy and other rapid-eye-movement sleep-related symptoms. 

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