Ropinirole hydrochloride

Ropinirole hydrochloride(SKF101468 hydrochloride) a selective dopamine D2 receptor inhibitor with IC50 of 29 nM.Target: Dopamine D2 ReceptorRopinirole (50 mg/kg, i.p.) causes biphasic spontaneous locomotor activity in mice. Ropinirole (0.05-1.0 mg/kg SC) dose-dependently inhibits the dyskinesias induced by 2-di-n-propylamino-5,6-di-hydroxytetralin in mice. Ropirtirole, at doses of 1 and 10 μg, injected unilaterally directly into the striatum of the rat causes marked, contralateral (away from the side of injection) asymmetry and circling in mice. Ropinirole (0.05-1.0 mg/kg SC or 0.1 mg/kg PO) reverses all motor and behavioural deficits induced by MPTP in marmosets [1]. Ropinirole (2 mg/kg, i.p.) for 7 days increases GSH, catalase and SOD activities in the striatum and protected striatal dopaminergic neurons against 6-hydroxydopamine (6-OHDA) in mice [2]. Ropinirole (0.2 mg/kg, i.p.) improves the use of previously akinetic forelimb and produced robust circling behavior in lesioned rats with striatal over-expression of both D2R and D3R compared to lesioned animals that received blank vector. The subtherapeutic dose of ropinirole generates only modest motor effects in lesioned rats with sole over-expression of D2R or D3R [3]. Ropinirole (1-8 mg t.i.d.) is rapidly and completely absorbed with oral bioavailability of 55%, clearance of 780 mL/min, elimination half-life of 6 hours in healthy volunteer. Since the major route of elimination for Ropinirole is by the CYP enzyme system, mainly by CYP1A2 and also by CYP3A4, inhibition of the former and possibly the latter may reduce the agent's clearance and lead to drug accumulation [4].

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

[1]. Eden, R.J., et al., Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist. Pharmacol Biochem Behav, 1991. 38(1): p. 147-54.

[2]. Iida, M., et al., Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res, 1999. 838(1-2): p. 51-9.

[3]. Lam, Y.W., Clinical pharmacology of dopamine agonists. Pharmacotherapy, 2000. 20(1 Pt 2): p. 17S-25S.

[4]. Allen, R., et al., Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome. Sleep, 2004. 27(5): p. 907-14.

CB-154 mesylate | SCH 23390 hydrochloride | Levodopa | Cabergoline | Thioridazine hydrochloride | Brexpiprazole | Domperidone | Trifluoperazine dihydrochloride | pimozide | Risperidone | SKF38393 HCl | Cariprazine | SERTINDOLE | Fluphenazine (dihydrochloride) | Nomifensine

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

396 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1725,199

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

71 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1725,199 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1500 mg/kg/30D-I

TOXIC EFFECTS :

Liver - changes in liver weight Endocrine - changes in adrenal weight Related to Chronic Data - changes in ovarian weight

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1731,199

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

18250 mg/kg/1Y-I

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Kidney, Ureter, Bladder - other changes Endocrine - changes in adrenal weight

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1731,199

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

450 mg/kg/30D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Behavioral - excitement Skin and Appendages - hair

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1741,199

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

5475 mg/kg/1Y-I

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - changes in ovarian weight Related to Chronic Data - changes in testicular weight

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1741,199 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3040 mg/kg

SEX/DURATION :

female 2 week(s) pre-mating - 20 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1747,199

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1747,199

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

280 mg/kg

SEX/DURATION :

female 15-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 24(Suppl 11),S1747,199