Risperidone

Risperidone is a serotonin 5-HT2 receptor blocker, P-Glycoprotein inhibitor and potent dopamine D2 receptor antagonist, with Kis of 4.8, 5.9 nM for 5-HT2A and dopamine D2 receptor, respectively.

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

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

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Signaling Pathways >> Membrane Transporter/Ion Channel >> P-glycoprotein

Research Areas >> Neurological Disease

5-HT2A Receptor:4.8 nM (Ki)

dopamine D2 receptor:5.9 nM (Ki)

P-Glycoprotein

Risperidone is a serotonin 5-HT2 receptor blocker, P-Glycoprotein inhibitor and potent dopamine D2 receptor antagonist, with Kis of 4.8, 5.9 nM for 5-HT2A and dopamine D2 receptor, respectively. Risperidone dose-dependently inhibited the release of IL-12 in mature DCs, while the production of IL-10 is dose-dependently increased by Risperidone. A high dose of risperidone can induce TNF-α release from mature DCs[3].

In the first experiment, body weight is found to be slightly but significantly lower in the Risperidone-treated rats as a function of age. Similar to the first experiment, age-dependent differences in body weight are also observed between the three treatment groups in the second locomotor experiment. Rats treated with the 3.0 mg/kg dose of Risperidone weigh less than vehicle-treated rats on postnatal days 35, 38, and 41. The third locomotor experiment involves larger, mixed-sex litters in contrast to the smaller, single-sex litters used in the first two experiments. As noted for the first two experiments, rats treated with Risperidone in the third experiment gain less weight in an age-dependent manner[4].

Rats[4] A total of 211 Long-Evans rats (56 females and 155 males) are used. Within each study, three groups of roughly equal numbers of rats receive injections of 1.0 mg/kg of Risperidone, 3.0 mg/kg of Risperidone, or the vehicle used for the Risperidone solution as a control. In the first experiment, twenty-six male rats (n=9 in the vehicle and 3.0 mg/kg Risperidone groups; n=8 in the 1.0 mg/kg Risperidone group) are tested for locomotor activity for 20 minutes a day beginning at postnatal day 49 and continuing daily until postnatal day 53. A second experiment determined if the locomotor effects of early-life Risperidone treatment persisted well into adulthood. A third experiment ascertains the effects of sex on the locomotor effects of early-life Risperidone seen in young adult rats. In this experiment, sixty male (n=20 per treatment group) and 56 female (n=19 rats in the vehicle and 3.0 mg/kg dose group, n=18 in the 1.0 mg/kg dose group) rats are treated. A fourth experiment assessed reversal learning during adulthood in rats administered earlylife risperidone. Forty-two male rats (n=14 per treatment group) are treated[4].

[1]. Nyberg S, et al. 5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperidone. Psychopharmacology (Berl). 1993;110(3):265-72.

[2]. Zhu HJ, et al. Risperidone and paliperidone inhibit p-glycoprotein activity in vitro. Neuropsychopharmacology. 2007 Apr;32(4):757-64.

[3]. Chen ML, et al. Risperidone modulates the cytokine and chemokine release of dendritic cells and induces TNF-α-directed cell apoptosis in neutrophils. Int Immunopharmacol. 2012 Jan;12(1):197-204.

[4]. Bardgett ME, et al. Adult rats treated with risperidone during development are hyperactive. Exp Clin Psychopharmacol. 2013 Jun;21(3):259-67.

elacridar | Harmine | Valspodar | CB-154 mesylate | Pimavanserin | SCH 23390 hydrochloride | Levodopa | Tariquidar | Zosuquidar trihydrochloride | Cabergoline | Serotonin hydrochloride | Sodium Ferulate | Thioridazine hydrochloride | Brexpiprazole | Domperidone

MOLECULAR FORMULA :

C23-H27-F-N4-O2

MOLECULAR WEIGHT :

410.54

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3428 ug/kg

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Cardiac - EKG changes not diagnostic of specified effects Nutritional and Gross Metabolic - changes in sodium

REFERENCE :

AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 22,1908,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

429 ug/kg/15D-I

TOXIC EFFECTS :

Brain and Coverings - changes in surface EEG Behavioral - anorexia (human) Behavioral - alteration of operant conditioning

REFERENCE :

JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 58,323,1997

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

114 ug/kg/2D-I

TOXIC EFFECTS :

Behavioral - wakefulness Behavioral - euphoria Behavioral - excitement

REFERENCE :

AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 153,1234,1996

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

56600 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 244,685,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

98 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,2991,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

34300 ug/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,2991,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

63100 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 244,685,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

26900 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 244,685,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

18300 ug/kg

TOXIC EFFECTS :

Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory stimulation Gastrointestinal - hypermotility, diarrhea

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,2991,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

14100 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 244,685,1988 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

228 mg/kg/13W-I

TOXIC EFFECTS :

Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,2991,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2738 mg/kg/1Y-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - other changes Endocrine - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,2991,1993 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

110 mg/kg

SEX/DURATION :

female 8-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,3023,1993