| Bioactivity | GBR 12935 is a potent, and selective dopamine reuptake inhibitor, with the binding constant (Kd) of 1.08 nM in COS-7 cells. GBR 12935 stimulates the locomotion activity in different mice strains but fails to induce stereotypy. Thus, GBR 12935 also prevents the d-Fenfluramine-induced head-twitch response in mice[1][2][3][4]. |
| Invitro | GBR 12909 (10-100 nM) also shows a high affinity for CYP2D6 with the Kd value of 42.2 nM, lower than the affinity for dopamine transporter. The binding effect can be reduced by Quinidine (HY-B1751) and Quinine (HY-D0143), which are the specific and potent inhibitors of CYPZD enzymatic activities[1].GBR 12935 (10 nM; 2 min) increases the extracellular levels of dopamine to approximately 400% of basal during the application in the nucleus accumbens[2].GBR 12935 (100 μM; 60 min) increases extracellular levels of dopamine compared with levels for artificial cerebrospinal fluid (ACSF) by local perfusion for 60 min[2].GBR 12935 (1-9 nM) dose-dependently inhibits active uptake of [3H]dopamine in homogenates of the nucleus accumbens[2].Co-perfusion of 100 μM GBR 12935 with either 100 μM Sulpiride (HY-B1019) or Raclopride (HY-103414) produces a significant reduction in the GBR 12935 induced increase in the extracellular levels of dopamine to basal levels[2]. |
| In Vivo | GBR 12935 (1-32 mg/kg; repeat injection; 7 d) elevates locomotion activity to a greater extent in C57BL/6J mice than DBA/2J mice, and (10 mg/kg; injection; 7 d) results few mice sensitized to cocaine-induced stereotypy with repeated injections[3]. Animal Model: |
| Name | GBR 12935 |
| CAS | 76778-22-8 |
| Formula | C28H34N2O |
| Molar Mass | 414.58 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. Hiroi T, et al. Specific binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl propyl) piperazine (GBR-12935), an inhibitor of the dopamine transporter, to human CYP2D6. Biochem Pharmacol. 1997 Jun 15;53(12):1937-9. [2]. Rahman S, et al. Negative interaction of dopamine D2 receptor antagonists and GBR 12909 and GBR 12935 dopamine uptake inhibitors in the nucleus accumbens. Eur J Pharmacol. 2001 Feb 23;414(1):37-44. [3]. Tolliver BK, et al. Comparison of cocaine and GBR 12935: effects on locomotor activity and stereotypy in two inbred mouse strains. Pharmacol Biochem Behav. 1994 Jul;48(3):733-9. [4]. Darmani NA. Cocaine and selective monoamine uptake blockers (sertraline, nisoxetine, and GBR 12935) prevent the d-fenfluramine-induced head-twitch response in mice. Pharmacol Biochem Behav. 1998 May;60(1):83-90. |