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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by michael on March 22, 2001, at 21:38:07
Andrew,
Another interesting article. I don't know if maybe you've already seen these two abstracts...?
It seems like pramipexole (mirapex) - a dopamine agonist - is acting like an antipsychotic? Am I getting this right? Or am I missing the boat here? I'm a little confused...
Just curious for your (and anyone else - Scott's/Cam's/Etc.) interpretation, once again. michael
----------------------------------------------------Eur J Pharmacol 1997 Apr 11;324(1):31-7 Related Articles, Books
The behavioural effects of pramipexole, a novel dopamine receptor agonist.Maj J, Rogoz Z, Skuza G, Kolodziejczyk K
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydroc hlo ride) is a novel dopamine D2 family receptor agonist with a predominant action on D2 autoreceptors and with some D3 vs. D2 receptor preference. The central behavioural effects of pramipexole given subcutaneously to rats (male Wistar) and mice (Albino Swiss) are presented in this paper. Used in low doses (0.001-0.1 mg/kg), pramipexole induced locomotor hypoactivity which was antagonized by a low dose of spiperone; at higher doses (0.3, 1 mg/kg) it evoked hyperactivity which was inhibited by haloperidol, sulpiride and clozapine, but not by SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride). Pramipexole (0.1-1.0 mg/kg) antagonized the akinesia induced by combined pretreatment with reserpine (5 mg/kg) and alpha-methyl-p-tyrosine (250 mg/kg). Pramipexole (0.1-1 mg/kg) potentiated the hyperkinetic effect of L-DOPA (L-3,4-dihydroxyphenylalanine) (50 and 200 mg/kg, together with benserazide, 50 mg/kg) in naive and monoamine-depleted (reserpine + alpha-methyl-p-tyrosine) rats. The higher doses of pramipexole (1 and 3 mg/kg) evoked stereotypy which was antagonized by pretreatment with sulpiride or clozapine. The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg). Pramipexole (1 mg/kg) induced hypothermia in mice, which was antagonized by sulpiride. The obtained results indicate that pramipexole: (i) at low doses stimulates the dopamine D2 presynaptic autoreceptors; (ii) at higher doses stimulates dopamine D2 postsynaptic receptors. An effect on the dopamine D3 receptor cannot be excluded. At low doses pramipexole may have antipsychotic activity, and at higher ones antiparkinsonian activity.
PMID: 9137910
Posted by michael on March 22, 2001, at 23:48:35
In reply to Andrew, re: mirapex... one more time, posted by michael on March 22, 2001, at 21:38:07
> Andrew,
>
> Another interesting article. I don't know if maybe you've already seen these two abstracts...?
>
> It seems like pramipexole (mirapex) - a dopamine agonist - is acting like an antipsychotic? Am I getting this right? Or am I missing the boat here? I'm a little confused...
>
> Just curious for your (and anyone else - Scott's/Cam's/Etc.) interpretation, once again. michael
>
>
> ----------------------------------------------------
>
>
>
>
>
> Eur J Pharmacol 1997 Apr 11;324(1):31-7 Related Articles, Books
>
>
> The behavioural effects of pramipexole, a novel dopamine receptor agonist.
>
> Maj J, Rogoz Z, Skuza G, Kolodziejczyk K
>
> Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
>
> Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydroc hlo ride) is a novel dopamine D2 family receptor agonist with a predominant action on D2 autoreceptors and with some D3 vs. D2 receptor preference. The central behavioural effects of pramipexole given subcutaneously to rats (male Wistar) and mice (Albino Swiss) are presented in this paper. Used in low doses (0.001-0.1 mg/kg), pramipexole induced locomotor hypoactivity which was antagonized by a low dose of spiperone; at higher doses (0.3, 1 mg/kg) it evoked hyperactivity which was inhibited by haloperidol, sulpiride and clozapine, but not by SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride). Pramipexole (0.1-1.0 mg/kg) antagonized the akinesia induced by combined pretreatment with reserpine (5 mg/kg) and alpha-methyl-p-tyrosine (250 mg/kg). Pramipexole (0.1-1 mg/kg) potentiated the hyperkinetic effect of L-DOPA (L-3,4-dihydroxyphenylalanine) (50 and 200 mg/kg, together with benserazide, 50 mg/kg) in naive and monoamine-depleted (reserpine + alpha-methyl-p-tyrosine) rats. The higher doses of pramipexole (1 and 3 mg/kg) evoked stereotypy which was antagonized by pretreatment with sulpiride or clozapine. The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg). Pramipexole (1 mg/kg) induced hypothermia in mice, which was antagonized by sulpiride. The obtained results indicate that pramipexole: (i) at low doses stimulates the dopamine D2 presynaptic autoreceptors; (ii) at higher doses stimulates dopamine D2 postsynaptic receptors. An effect on the dopamine D3 receptor cannot be excluded. At low doses pramipexole may have antipsychotic activity, and at higher ones antiparkinsonian activity.
>
> PMID: 9137910
Posted by AndrewB on March 22, 2001, at 23:50:31
In reply to Andrew, re: mirapex... one more time, posted by michael on March 22, 2001, at 21:38:07
Michael,
It to be expected that at low doses Pramipexole acts as an antipsychotic and an AD at higher doses, just as the inverse is true of amisulpride. The dosages recommended for its use as an AD (i.e. 5mg./day) are high doses and it definatley doesn't act as an antipsych. at those doses.
Just one note, the presynaptic autoreceptors have a stronger binding affinity than the postsynaptic, but they get filled up with rather small does of a D2/D3 meds. That is why at low doses amisulpride and pramipexole latch onto the autoreceptors but at higher doses those receptors are full and the meds then start hitting the postsynaptic receptors.
AndrewB
Posted by michael on March 22, 2001, at 23:55:08
In reply to Re: Andrew, re: mirapex... one more time, posted by AndrewB on March 22, 2001, at 23:50:31
> Michael,
>
> It to be expected that at low doses Pramipexole acts as an antipsychotic and an AD at higher doses, just as the inverse is true of amisulpride. The dosages recommended for its use as an AD (i.e. 5mg./day) are high doses and it definatley doesn't act as an antipsych. at those doses.
>
> Just one note, the presynaptic autoreceptors have a stronger binding affinity than the postsynaptic, but they get filled up with rather small does of a D2/D3 meds. That is why at low doses amisulpride and pramipexole latch onto the autoreceptors but at higher doses those receptors are full and the meds then start hitting the postsynaptic receptors.
>
> AndrewB
Posted by michael on March 23, 2001, at 0:16:10
In reply to Thanks Andrew (np), posted by michael on March 22, 2001, at 23:55:08
Eur J Pharmacol 1991 Jul 23;200(1):65-72 Related Articles, Books
Pramipexole, a dopamine D2 autoreceptor agonist, decreases the extracellular concentration of dopamine in vivo.Carter AJ, Muller RE
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim, F.R.G.
Pramipexole (SND 919) is a dopamine D2 autoreceptor agonist which is structurally related to talipexole (B-HT 920), a potential antipsychotic agent. The aim of this study was to investigate the effects of pramipexole on the extracellular concentration of dopamine in vivo. Dopamine and its metabolites, 3,4-dihydrophenylacetic acid and homovanillic acid, were measured in the anterior striatum of freely moving rats by microdialysis and high-performance liquid chromatography with electrochemical detection. Pramipexole (30 and 100 micrograms/kg) caused long-lasting decreases in the extracellular concentrations of dopamine and its metabolites. Talipexole (30 micrograms/kg) produced similar effects. Sulpiride (5 mg/kg), a selective dopamine D2 antagonist, caused a transient increase in the concentration of dopamine and long-lasting increases in the concentrations of its metabolites; it also reversed the effects of pramipexole. SCH-23390 (100 micrograms/kg), a selective dopamine D1 receptor antagonist, caused a transient increase in the concentration of dopamine but did not affect the concentrations of the metabolites. SCH-23390 failed to reverse the effects of pramipexole. These results indicate that pramipexole reduces the extracellular concentrations of dopamine and its metabolites in vivo through a reversible interaction with the dopamine D2 receptor.
PMID: 1685123
> Michael,
> >
> > It to be expected that at low doses Pramipexole acts as an antipsychotic and an AD at higher doses, just as the inverse is true of amisulpride. The dosages recommended for its use as an AD (i.e. 5mg./day) are high doses and it definatley doesn't act as an antipsych. at those doses.
> >
> > Just one note, the presynaptic autoreceptors have a stronger binding affinity than the postsynaptic, but they get filled up with rather small does of a D2/D3 meds. That is why at low doses amisulpride and pramipexole latch onto the autoreceptors but at higher doses those receptors are full and the meds then start hitting the postsynaptic receptors.
> >
> > AndrewB
Posted by PhoenixGirl on March 23, 2001, at 15:45:49
In reply to Re: Andrew, re: mirapex... one more time, posted by AndrewB on March 22, 2001, at 23:50:31
I've never understood this. It's an antipsychotic, so it ought to be a dopamine antagonist. But others have said that it's dopaminergic. Is is dopaminergic at low doses, and a dopamine antagonist at higher doses?
Posted by Lorraine on March 24, 2001, at 1:10:16
In reply to Re: Andrew, re: mirapex... one more time, posted by AndrewB on March 22, 2001, at 23:50:31
Andrew: You posted a while back about my Selegiline (which was a 10 mg) being scaled back to 5 mg/day. I have done this and added 2.5 mg dexidrine. In addition, I am taking 300 mg of Neurontin 3x day. This is day one of this combo and, you know, the day went pretty well. I think you were right about the Selegiline impacting the anxiety. For one day only, I tried augmenting 10 mg Selegiline, 900 mg Neurontin with .125 Mirapex. Really felt wiped out. Funny, I thought the Mirapex would be activating. No so, at least at this dose. Also felt like I would fall asleep at the wheel--which I know can be a side effect of Mirapex--don't know if it gets better over time. I know I didn't give the Mirapex an adequate trial--I'm leaving on vacation and it was more important to have something workable in place than to do it right. Maybe when I return I'll give it a better trail. I think I've read that Mirapex needs a little time before its effects are apparent. Actually, the Neurontin, dexedrine, Selegiline cocktail is not bad, but I still have the physical anxiety (tightness in chest, difficulty taking a deep breath). Maybe time to add some Pindolol to the mix. In the drug intereactions on Dr. Koop, I had read that Neurontin and Mirapex have a mild interaction and my wiped out feeling my have been Mirapex enhancing the Neurontin--so it might have smoothed out over time. Just wanted to let you know what's going on with my meds since our meds seems to be overlapping a bit and to thank you for the tip on cutting back the Selegiline, although I couldn't have done the without the dexedrine addition.
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