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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by jms600 on January 1, 2004, at 16:16:23
Does anyone know of any stimulating drugs which block dopamine and the reuptake of noradrenaline?
Posted by linkadge on January 1, 2004, at 16:33:05
In reply to Stimulants with Dopamine Noradrenaline effects??, posted by jms600 on January 1, 2004, at 16:16:23
Ritalin does so.
Linkadge
Posted by SLS on January 1, 2004, at 16:55:13
In reply to Stimulants with Dopamine Noradrenaline effects??, posted by jms600 on January 1, 2004, at 16:16:23
> Does anyone know of any stimulating drugs which block dopamine and the reuptake of noradrenaline?
I think any of the amphetamines will do this. However, their major effect is to increase the release of the neurotransmitters.
- Scott
Posted by tenshen on January 1, 2004, at 17:22:31
In reply to Re: Stimulants with Dopamine Noradrenaline effects??, posted by SLS on January 1, 2004, at 16:55:13
Adderall
Posted by SLS on January 1, 2004, at 17:42:33
In reply to Re: Stimulants with Dopamine Noradrenaline effects??, posted by SLS on January 1, 2004, at 16:55:13
> > Does anyone know of any stimulating drugs which block dopamine and the reuptake of noradrenaline?
>
> I think any of the amphetamines will do this. However, their major effect is to increase the release of the neurotransmitters.Almost forgot:
mazindol (Mazinor, Sanorex)
sibutramine (Meridia)
- Scott
Posted by scott-d-o on January 1, 2004, at 20:17:17
In reply to Re: Stimulants with Dopamine Noradrenaline effects??, posted by tenshen on January 1, 2004, at 17:22:31
Perhaps a more relevant question is, what psychostimulants don't affect these neurotrasmitters? Even caffeine has an effect on them, albeit an indirect one.
After all, what makes a med "stimulating" is caused by epinephrine (adrenalin) agonising beta-adrenergic receptors in the heart, thus increasing heart rate and blood pressure.
Posted by Shawn. T. on January 1, 2004, at 22:11:06
In reply to Re: Stimulants with Dopamine Noradrenaline effect, posted by scott-d-o on January 1, 2004, at 20:17:17
A drug can be "stimulating" in a number of ways; the stimulation mediated by epinephrine in the heart is sympathetic stimulation rather than psychomotor stimulation or some other type of stimulation. The word "psychostimulant" seems to have become associated with drugs that increase dopamine concentrations in the striatum. For example, the norepinephrine reuptake inhibitor atomoxetine (Strattera) isn't considered a stimulant even though it can induce stimulating effects in some people. Atomoxetine can inhibit dopamine reuptake in the prefrontal cortex because the dopamine in this region is transported primarily by the norepinephrine transporter; therefore, psychostimulants are linked to increased dopamine levels in a specific region of the brain (regions of the striatum like the nucleus accumbens).
I think that it is important to note that Ritalin (methylphenidate) inhibits dopamine reuptake transporters more potently than it inhibits norepinephrine transporters (it is roughly 5 times more potent ... see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7851480&dopt=Abstract ). It's important to consider this fact when comparing Ritalin with Strattera; do not assume that the two affect norepinephrine reuptake equally.
Another well-known psychostimulant that blocks dopamine and norepinephrine reuptake is cocaine; it also inhibits the serotonin transporter to a lesser degree.
Drugs in clinical trials that inhibit the reuptake of dopamine, norepinephrine, and serotonin include Sepracor's (R)-sibutramine metabolite (phase II; see http://www.sepracor.com/science/index.cfm?s=2B ), DOV's DOV 216,303 (phase II; see http://www.dovpharm.com/sub_page/product_dov216303.html ), and DOV's DOV 21,947 (phase I).
GSK's GW353162 is a dopamine and norepinephrine reuptake inhibitor in phase I clinical trials. I believe that Pfizer has a dopamine, norepinephrine, and serotonin reuptake inhibitor in phase II, but I don't know the name of the drug. There are likely several others being investigated.
Shawn
Posted by Omega Woman on January 2, 2004, at 3:00:15
In reply to Stimulants with Dopamine Noradrenaline effects??, posted by jms600 on January 1, 2004, at 16:16:23
> Does anyone know of any stimulating drugs which block dopamine and the reuptake of noradrenaline?
I just tried some amisulperide, which blocks dopamine. It definitly reduces psychotic obsessions.
Posted by scott-d-o on January 2, 2004, at 16:08:58
In reply to Re: Stimulants with Dopamine Noradrenaline effect, posted by Shawn. T. on January 1, 2004, at 22:11:06
> The word "psychostimulant" seems to have become associated with drugs that increase dopamine concentrations in the striatum. Atomoxetine can inhibit dopamine reuptake in the prefrontal cortex because the dopamine in this region is transported primarily by the norepinephrine transporter; therefore, psychostimulants are linked to increased dopamine levels in a specific region of the brain (regions of the striatum like the nucleus accumbens).
I have to disagree here. Increases in dopamine in the nucleus accumbens are associated more with a "pleasurable effect" rather than a "stimulating" one. Heroin and other opiates cause massive increases in dopamine here and are far from psychostimulants.
Antipsychotics such as sulpiride and amisulpride increase dopamine release in the striatum by antagonising D2 and D3 autoreceptors located there, however they are not classified as "psychostimulants." Here's a reference for you which indicates amisulpride occupies 56% of these receptors in the striatum at the dosage used.
scott
Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? an in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients.Bressan RA, Erlandsson K, Jones HM, Mulligan R, Flanagan RJ, Ell PJ, Pilowsky LS.
British Association of Psychopharmacology, Harrogate, UK. r.bressan@iop.kcl.ac.uk
OBJECTIVE: Atypical antipsychotic drug treatment is clinically effective with a low risk of extrapyramidal symptoms. Explanations for the mechanism underlying this beneficial therapeutic profile of atypical over typical antipsychotic agents include 1) simultaneous antagonism of dopamine D(2) and serotonin 5-HT(2A) receptors or 2) selective action at limbic cortical dopamine D(2)-like receptors with modest striatal D(2) receptor occupancy. Amisulpride is an atypical antipsychotic drug with selective affinity for D(2)/D(3) dopamine receptors and provides a useful pharmacological model for examining these hypotheses. The authors' goal was to evaluate whether treatment with amisulpride results in "limbic selective" D(2)/D(3) receptor blockade in vivo. METHOD: Five hours of dynamic single photon emission tomography data were acquired after injection of [(123)I]epidepride (approximately 150 MBq). Kinetic modeling was performed by using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a healthy volunteer comparison group (N=6). RESULTS: Eight amisulpride-treated patients (mean dose=406 mg/day) showed moderate levels of D(2)/D(3) receptor occupancy in the striatum (56%), and significantly higher levels were seen in the thalamus (78%) and temporal cortex (82%). CONCLUSIONS: Treatment with amisulpride results in a similar pattern of limbic cortical over striatal D(2)/D(3) receptor blockade to that of other atypical antipsychotic drugs. This finding suggests that modest striatal D(2) receptor occupancy and preferential occupancy of limbic cortical dopamine D(2)/D(3) receptors may be sufficient to explain the therapeutic efficacy and low extrapyramidal symptom profile of atypical antipsychotic drugs, without the need for 5-HT(2A) receptor antagonism.
PMID: 12900302 [PubMed - indexed for MEDLINE]
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