(+)-Bicuculline

(+)-Bicucline ((+)-Bicucline )) is a competitive GABAA receptor antagonist with an IC₅₀ of 2μM ^[1]. (+)-Bicuculline also inhibits Ca²⁺-activated potassium channels ^[2]. (+)-Bicuculline reduces the effects of GABA without affecting the effects of glycine ^[3].

In vitro, (+)-Bicuculline (10 μM) treated primary cortical neuronal cells of rat E18 embryos for 15–60 min, enhanced neuronal synaptic NMDAR signaling, down-regulated STEP 61 expression, and accompanied the STEP substrate GluN 2B , increased tyrosine phosphorylation of Pyk 2 and ERK 1/2 ^[4]. (+)-Bicuculline (10μM) treatment of rat hippocampal neuron cells can cause calcium oscillations ^[5].

In vivo, (+)-Bicuculline (3.5mg/kg) treated Ovx rats via daily subcutaneous injection significantly reversed progesterone-induced cognitive decline and alleviated working memory impairment ^[6]. (+)-Bicuculline (1, 2, 4 mg/kg) affects the auditory steady-state response (ASSR) of SD rats through subcutaneous injection, dose-dependently reduces the ASSR signal, and significantly decreases within 10-30 minutes after administration Spectral Perturbation (ERSP) ^[7].

References:
[1]Collins M , Duke R , Huang S ,et al. Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant alpha1beta2gamma2L GABA(A) receptors.[J].European Journal of Pharmacology, 2003, 464(1):1-8.
[2]Khawaled R , Bruening-Wright A , Adelman J P ,et al.Bicuculline block of small-conductance calcium-activated potassium channels[J].Pflügers Archiv, 1999, 438(3):314-321.
[3]Johnston G A. Advantages of an antagonist: bicuculline and other GABA antagonists[J].British Journal of Pharmacology, 2013.
[4]Xu J1, Kurup P1, et al. Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP61 [J]. Mol Neurobiol. 2017.
[5]Maiorov S A, Kairat B K, Gaidin S G, et al. Activation of the Cannabinoid Receptors Suppresses Hyperexcitation of Rat Hippocampal Neuronal Networks In Vitro[J]. Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2023, 17(2): 169-175.
[6]Blair B B , Kingston M L , Koenig E N ,et al. The GABA_A antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats[J].Frontiers in Aging Neuroscience, 2015.
[7]Yamazaki M, Honda S, Tamaki K, et al. Effects of (+)-bicuculline, a GABAa receptor antagonist, on auditory steady state response in free-moving rats[J]. PLoS One, 2020, 15(7): e0236363.

(+)-荷包牡丹碱((+)-Bicuculline ))是一种竞争性GABA_A受体拮抗剂，IC₅₀为2μM^[1]。(+)-Bicuculline也抑制Ca²⁺激活的钾离子通道^[2]。(+)-Bicuculline降低了GABA的作用而不影响甘氨酸的作用^[3]。 

在体外，(+)-Bicuculline（10μM）处理大鼠E18胚胎的原代皮层神经元细胞15–60min，增强了神经元突触NMDAR信号传导，下调了STEP 61表达，并伴随STEP底物GluN 2B、Pyk 2和ERK 1/2的酪氨酸磷酸化的增加^[4]。(+)-Bicuculline（10μM）处理大鼠海马神经元细胞可引起钙震荡^[5]。

在体内，(+)-Bicuculline（3.5 mg/kg）通过每日皮下注射治疗Ovx大鼠，显著逆转了孕酮诱导的认知能力下降，减轻工作记忆障^[6]。(+)-Bicuculline（1、2 、 4 mg/kg）通过皮下注射影响SD大鼠的听觉稳态反应（ASSR），剂量依赖性地降低了ASSR信号，给药后10 -30分钟内显著降低了光谱扰动 (ERSP)^[7]。