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Limited Quantity USD 15-60
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Chemical Structure| 17780-75-5 Chemical Structure| 17780-75-5

Structure of Clorgyline HCl
CAS No.: 17780-75-5

Chemical Structure| 17780-75-5

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Clorgiline HCl is an irreversible and selective MAO-A inhibitor.

Synonyms: N-2,4-Dichlorophenoxypropyl-N-methylpropargylamine; Clorgyline (hydrochloride); Clorgyline hydrochloride

4.5 *For Research Use Only !

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Product Citations

Product Citations

Lizette Couto ;

Abstract: Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species (ROS) that promote oxidative stress leading to cellular damage, including DNA damage. Our investigation begins by establishing a cellular system that overexpresses a functional DAT (GFP-DATC2) and elucidating the role of DAT and DA in METH-induced nuclear DNA damage, with a focus on nuclear DNA double-stranded breaks (DSBs). DNA DSBs, which represent the most deleterious form of DNA damage, were measured using two classical and well established approaches namely, detection of phosphorylated H2AX (gH2AX) and the neutral comet assay. Immunohistochemistry (IHC) experiments reveal an increase in g-H2AX expression in METH-treated N2A GFP-DATC2 cells compared to control N2A GFP cells, highlighting the link between DAT expression and DNA DSB formation. IHC analyses also demonstrated that the DAT blocker GBR 12909 significantly reduces METH-induced DNA DSBs in GFP-DATC2 cells, providing further evidence of DAT's pivotal role in this genotoxic process. Interestingly, the DNA DSBs induced by exposing cells to low concentrations of METH were repaired after METH removal. Investigation using the comet assay to functionally characterize nuclear DNA DSBs shows that co-treatment with METH and inhibitors targeting cytoplasmic ROS production, from DA, such as N-acetyl-l-cysteine (NAC), substantially decreases METH-induced DNA DSBs. Also in regard to DA regulation such as, pargyline and tetrabenazine, inhibitors of monoamine oxidase B (MAO-B) and vesicular monoamine transporter 2 (VMAT2) respectively showed a strong inhibition of METH-induced DNA DSBs. Intriguingly, inhibition of monoamine oxidase A (MAO-A) on the other hand fails to elicit a similar effect, suggesting the distinctive contributions of MAO-B in this context. Our findings also shed light on L-DOPA's dual role in DNA damage, which includes a protective effect in preventing METH-induced DNA DSBs at low concentrations. In summary, our studies unravel the intricate mechanisms underpinning METH-induced DNA DSBs in N2A cells overexpressing DAT. Highlighting the central roles of DAT, DA, ROS, MAO-B, and VMAT2 in the genotoxic processes induced by METH. These insights into the molecular pathways of METH-induced DNA DSBs may guide future therapeutic strategies to mitigate the detrimental effects of METH abuse on genomic stability.

Keywords: methamphetamine ; DNA damage ; double stranded breaks ; dopamine ; substance use disorder ; comet assay

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Product Details of Clorgyline HCl

CAS No. :17780-75-5
Formula : C13H16Cl3NO
M.W : 308.63
SMILES Code : C#CCN(CCCOC1=CC=C(Cl)C=C1Cl)C.[H]Cl
Synonyms :
N-2,4-Dichlorophenoxypropyl-N-methylpropargylamine; Clorgyline (hydrochloride); Clorgyline hydrochloride
MDL No. :MFCD00052012

Safety of Clorgyline HCl

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H312+H332
Precautionary Statements:P280-P301+P310
Class:6.1
UN#:2811
Packing Group:

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
22RV1 cells 1 μM and 10 μM 21 days To test the effect of clorgyline on tumorigenesis and stemness, results showed reduction in colony forming ability of 22RV1 cells, but more resistant than LNCaP cells Oncogene. 2018 Sep;37(38):5175-5190
LNCaP cells 1 μM and 10 μM 21 days To test the effect of clorgyline on tumorigenesis and stemness, results showed significant reduction in colony forming ability of LNCaP cells Oncogene. 2018 Sep;37(38):5175-5190
LC neurons in rat midpontine brain slices 10 μM 22 min To investigate the effect of Clorgyline on the spontaneous firing rate of LC neurons, results showed that Clorgyline did not affect the spontaneous firing rate of LC neurons nor the stimulatory effect of 2-BFI. Br J Pharmacol. 1998 Dec;125(8):1685-94
guinea-pig proximal colon whole colon 1 μM 60 min To evaluate the effect of CGRP on 5-HT outflow in the presence of the monoamine oxidase A inhibitor clorgyline. CGRP elicited a concentration-dependent increase in 5-HT outflow from the whole colon, but not from mucosa-free muscle layer preparations. Br J Pharmacol. 2004 Feb;141(3):385-90

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rats Conscious rats Oral 2 mg/kg Single dose To study the effects of Clorgyline on cardiovascular responses to L-DOPA. Results showed that Clorgyline significantly potentiated the pressor response to the highest dose of L-DOPA (150 mg/kg) and caused a significant tachycardic response to the 100 mg/kg dose of L-DOPA. Br J Pharmacol. 2006 Nov;149(6):647-56
Adult male albino Sprague-Dawley rats Anesthetized rats Intraperitoneal injection 3 mg/kg Every 12 hours for 14 days To study the effect of chronic Clorgyline treatment on the firing rate of LC neurons, results showed that Clorgyline treatment significantly reduced the spontaneous firing rate of LC neurons and completely abolished the excitatory effect of 2-BFI. Br J Pharmacol. 1998 Dec;125(8):1685-94
Rats Sprague-Dawley rats Subcutaneous injection 2 mg/kg Once daily for 3, 6, or 13 days To evaluate the effect of MAOI pretreatment on the intensity of serotonin syndrome. Results showed that rats pretreated for 3 and 6 days exhibited more severe neuromuscular activity and body-core temperature abnormalities in response to challenge injection, whereas rats pretreated for 13 days did not show this intensified effect. Neuropsychopharmacology. 2014 Jul;39(8):1996-2007
Mice Pressure overload model (TAC) Intraperitoneal injection 1 mg/kg/day Once daily for 6 weeks To study the effect of Clorgyline on pressure overload-induced heart failure, results showed Clorgyline improved cardiac function and structure, reduced oxidative stress and cardiomyocyte apoptosis. Circ Res. 2010 Jan 8;106(1):193-202

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Preparing Stock Solutions 1mg 5mg 10mg

1 mM

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10 mM

3.24mL

0.65mL

0.32mL

16.20mL

3.24mL

1.62mL

32.40mL

6.48mL

3.24mL

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