Posted by undopaminergic on May 12, 2008, at 0:56:04
In reply to What are some dopameric and/or noradrengeric med?, posted by John Doughboy on May 11, 2008, at 16:37:55
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> Please help-the only ones I can think of are the amphetamines and methylpnenidate and that other ADD med Stattera (a selective NRI) , and some very nasty tricyclic AD's that are relatively NE specific.
>Atomoxetine (Strattera) and reboxetine (Edronax) are highly selective noradrenaline (NA) reuptake inhibitors. These can be used to test the role of NA.
There are no selective dopamine (DA) reuptake inhibitors, except certain research compounds and the discontinued amineptine. The closest you can get within the range of clinically available drugs is methylphenidate (MPH) - including dextromethylphenidate (Focalin). Although modafinil has relatively better selectivity for DA over NA in comparison with MPH, it's less potent. MPH and amphetamines (AMPH) are substantially different in their mode of action, so what applies to AMPH is not necessarily true for MPH. For example, AMPH depletes neuronal stores of DA (and probably NA), whereas reuptake inhibitors, such as MPH (and cocaine), enhance them. In other words, DA reuptake inhibitors are worth trying - for comparison if nothing else.
Sulpiride (SLP) and amisulpride (ASLP) are DA D2-/D3-receptor antagonists with preferential affinity for presynaptic autoreceptors. DA autoreceptor blockade enhances DA release from nerve terminals into the synapse. The resulting stimulant effects of low doses of SLP or ASLP may be more powerful than those of MPH, although the combination of both is even better.
Another class of dopaminergic agents are the direct agonists. Long-term use of the ergot-derived ones are best avoided, due to the risk of serious adverse consequences, including cardiac valvulopathy. Clinically available non-ergot DA agonists are pramipexole, ropinirole, quinagolide, piribedil, and apomorphine. Of these, only apomorphine (derived from morphine) has any significant affinity to D1-subtype receptors; however, it has a very short half-life and is generally not used orally. Pramipexole has the highest affinity to D3-receptors, and may be the most anti-anhedonic of the dopamine agonists. Ropinirole is quite similar to pramipexole; both of them have been associated with compulsive gambling and hypersexuality. Piribedil has alpha2-adrenergic antagonist properties, which may be detrimental or beneficial depending on the details of your situation. Quinagolide is mainly used against hyperprolactinaemia, and its use in CNS disorders is not extensively explored. A problem with all the dopamine agonists under discussion is their preferential affinity for presynaptic DA receptors, the stimulation of which leads to reduced synthesis and release of DA; this is generally the opposite of the desired result, and may explain some of the adverse effects associatd with DA direct agonists, such as somnolence, sometimes of a very sudden onset.
Another class of drugs that may be of use for enhancing dopaminergic neurotransmission is MAO-inhibitors. Of the unselective MAOIs, tranylcypromine is likely to be the most appropriate, but only if you're prepared to avoid foods and drugs that are known to interact adversely with MAOIs. The selective MAO-B inhibitors selegiline and rasagiline have the advantage of a lower - often insignificant - potential for dangerous interactions with foods and drugs unless the recommended dose is exceeded; while the recommended doses of these drugs are unlikely to produce effects sufficient for your purposes, they may enhance the effects of stimulants, autoreceptor-blockers and DA precursors as well as rendering phenylalanine and phenylethylamine (PEA) effective as pharmacological agents.
The DA precursors are, of course, tyrosine and L-dopa. They are most useful when taken with peripheral inhibitors of aromatic amino acid decarboxylase (AADC) - of which carbidopa and benserazide are clinically relevant - in order to reduce peripheral side effects (e.g. nausea) and improve the availability of the DA precursor to the CNS; most preparations of L-dopa include a standard proportion of an AADC inhibitor.
Finally, some NMDA-antagonists, such as amantadine and especially memantine, can be useful to enhance dopaminergic neurotransmission - or so it would seem, based on their observed effects. These agents may have stimulant-like and anti-anhedonic effects of their own, but also appear to be useful for preventing tolerance to the beneficial effects of stimulants.
poster:undopaminergic
thread:828365
URL: http://www.dr-bob.org/babble/neuro/20080418/msgs/828629.html