The results show that ropinirole is a full agonist at human D2, D3 and D4 dopamine receptors. SKF-104557 the major human metabolite of ropinirole, had similar radioligand binding affinities to, but lower functional potencies than, the parent compound.
Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist
R.J. Edena, B. Costall*, A.M. Domeney*, P.A. Gerrard*, C.A. Harveya, M.E. Kelly*, R.J. Naylor*, D.A.A. Owena and A. Wrighta, 1
aSmithKline Beecham Research, The Frythe, Welwyn, Herts, England
*Neuropharmacology Research Group, University of Bradford, Bradford, West Yorkshire, England
Received 23 July 1990. Available online 7 November 2002.
These studies characterise the pharmacology of ropinirole, a selective D-2 agonist. High-affinity human caudate binding revealed a Ki for D2 receptors of 2.9 × 10−8 M with no affinity for D1 at 10−4 M in the rat. Ropinirole was weakly active at α2-adrenoceptors and 5-HT2 receptors but inactive at 5-HT1, benzodiazepine and gamma-aminobu acid receptors or α1 and β-adrenoceptors. In rodents, ropinirole, like apomorphine, caused biphasic spontaneous locomotor activity and contralateral circling in 6-OHDA-lesioned mice with no tolerance to the latter after 14 days treatment. Amphetamine caused ipsilateral responses in the lesioned mice. Ropinirole did not cause marked stereotypies. In marmosets ropinirole (0.05–1.0 mg/kg SC or 0.1 mg/kg OPO) reversed all motor and behavioral deficits induced by MPTP. This response started 10–20 minutes after dosing, and exceeded 2 hours. No tolerance was seen following chronic b.i.d. treatment. Similar results were obtained with 1-dopa plus benserazide; however, 1-dopa always caused emesis, whereas beneficial effects were shown with ropinirole in the absence of this side effect. These results support the continued clinical assessment of ropinirole for the treatment of Parkinson's disease.
Psychopharmacology (Berl). 2000 Jul;151(1):91-7.
Anxiolytic profile of ropinirole in the rat, mouse and common marmoset.
Rogers DC, Costall B, Domeney AM, Gerrard PA, Greener M, Kelly ME, Hagan JJ, Hunter AJ.
Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Derek_C_Rogers@sbphrd.com
RATIONALE: Some features of Parkinson's disease are exacerbated by stress and anxiety and it is important to understand the effects of dopamine receptor agonists on measures of anxiety. The aim of this study was to assess the effects of the dopamine D2/D3 receptor agonist ropinirole in models of anxiety and depression in the rat, mouse and marmoset. RESULTS: In the rat elevated plus-maze test, ropinirole (0.01-1 mg/kg, i.p.) produced an inverted-U dose-response curve in the percentage time spent in the open arms. Compared with vehicle, ropinirole (0.1 mg/kg) had a significant anxiolytic-like effect, which was similar to that observed with 1.5 mg/kg diazepam. This effect was found at doses that did not affect motor behaviour or induce stereotypy. In the mouse black and white box test of anxiety, ropinirole (0.1-10 mg/kg, i.p.) increased both the rearing time and number of line crosses in the white section. This effect reached statistical significance for both measures at a dose of 0.1 mg/kg and suggests an anxiolytic-like action of the compound. By contrast, the dopamine agonist bromocriptine (0.1-10 mg/kg, i.p.) did not produce significant changes in these behaviours. In the marmoset human threat test, ropinirole (0.01-10 microg/kg, s.c.) reduced the number of postures at all doses tested and this reached statistical significance at 10 microg/kg. Ropinirole did not compromise the effect of amitriptyline in the Porsolt test of depression and in itself produced antidepressant-like effects. CONCLUSIONS: These data demonstrate that systemic administration of ropinirole produces anxiolytic-like effects in three separate models in the mouse, rat and marmoset. This may predict an action of ropinirole in man that would provide a superior profile of action over other presently available anti-parkinsonian agents.
Full agonist at D4 receptors wich could make a potential very potent cognitive enhancer and an effective med for ADD, a anxiolytic profile wich isnt seen with other dopamine agonist and its dirt cheap and easy to get unlike lisuride and rotigotine.
This one looks far superior then pramipexole to me, from what i remember i think the anecdotal reports regarding this one where more positive, but i'l collect then anecdotal reports i can find tomorrow, i'm about to drop dead from working in the sun all day right now.
It has been shown to be effective against antidepressant induced sexual dysfunctioning, so adding it to a SSRI may reduce the side effects while at the same time reduce anxiety further.
Ropinirole for antidepressant-induced sexual dysfunction
Worthington JJ, Simon NM, Korbly NB,
Perlis RH, Pollack MH;
For the Anxiety Disorders Research Program.
Int Clin Psychopharmacol 2002 Nov;17(6):307-10
Sexual dysfunction is a relatively common side-effect of antidepressants, occurring in approximately one-half of patients, and is associated with significant distress and treatment non-compliance. Dopaminergic agents have been reported to be helpful for the treatment of antidepressant-induced sexual dysfunction and, in this report, we examined the efficacy of the dopamine agonist ropinirole for this indication. Thirteen patients (three women, 10 men), aged 42.6 +/- 7.7 years, who reported sexual dysfunction on a stable dose of antidepressant, were treated openly with ropinirole initiated at 0.25 mg/day and titrated up to 2-4 mg/day over 4 weeks, as tolerated. Ten of the 13 took ropinirole for at least 4 weeks, one discontinued due to an adverse event and two because of lack of response. Sexual dysfunction, as assessed by the Arizona Sexual Experience Scale scores, was reduced from 18.8 +/- 3.6 to 13.8 +/- 4.3 after 4 weeks on ropinirole at a mean dose of 2.1 mg/day. Overall, seven of 13 patients (54%) were rated as responders on the Clinical Global Impression of Improvement Scale. The addition of ropinirole may represent a potentially useful treatment strategy for antidepressant-induced sexual dysfunction.