AM1710 / MAKScientific, Tetra Bio-Pharma - LARVOL DELTA

Cannabinoid CB2 receptors in primary sensory neurons are implicated in CB2 agonist-mediated suppression of paclitaxel-induced neuropathic nociception and sexually-dimorphic sparing of morphine tolerance. (PubMed, Biomed Pharmacother) - "Anti-allodynic effects of structurally distinct CB2 agonists (LY2828360 and AM1710) were present in paclitaxel-treated CB2f/f mice and in mice lacking CB2 receptors in CX3CR1 expressing microglia/macrophages (CX3CR1CRE/+; CB2f/f), but were absent in mice lacking CB2 receptors in peripheral sensory neurons (AdvillinCRE/+; CB2f/f). LY2828360 (3 mg/kg per day i.p. x 8 days) delayed, but did not prevent, the development of paclitaxel-induced mechanical or cold allodynia in either CB2f/f or CX3CR1CRE/+; CB2f/f mice of either sex. Our findings have potential clinical implications."

Journal • Oncology • Pain • CX3CR1

Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats. (PubMed, Int J Mol Sci) - "Diabetic rats [streptozotocin (STZ)-induced] were treated topically (20 μL, 10 mg/mL), once daily for fourteen days (early stage DR model), with SR141716 (CB1R antagonist), AM1710 (CB2R agonist), and the dual treatment SR141716/AM1710. These findings provide new knowledge regarding the differential efficacies of the cannabinoids, when administered topically, in the treatment of ESDR. Cannabinoid neuroprotection of the diabetic retina in ESDR may prove therapeutic in delaying the development of the advanced stage of the disease."

Journal • Preclinical • CNS Disorders • Diabetes • Diabetic Retinopathy • Immunology • Inflammation • Metabolic Disorders • Retinal Disorders

Peripheral sensory neuron CB2 cannabinoid receptors are necessary for both CB2-mediated antinociceptive efficacy and sparing of morphine tolerance in a mouse model of anti-retroviral toxic neuropathy. (PubMed, Pharmacol Res) - "Antinociceptive efficacy of both AM1710 and LY2828360, but not reference analgesics, were absent in advillin;CB2 mice, which exhibited robust ddC-induced neuropathy. The present studies indicate that CB2 activation may alleviate HIV-associated antiretroviral neuropathy and identify a previously unreported mechanism through which CB2 activation produces antinociceptive efficacy. Our results also provide the first evidence that a CB2 agonist can reverse established morphine tolerance and demonstrate that CB2 localized to peripheral sensory neurons mediates the opioid tolerance sparing efficacy of CB2 agonists."

Journal • Preclinical • Human Immunodeficiency Virus • Immunology • Infectious Disease • Neuralgia • Pain • Peripheral Neuropathic Pain • CCL2 • IL1B • TNFA

A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse. (PubMed, Pain) - "Structurally distinct CB2 agonists (AM1710 and LY2828360) suppressed paclitaxel-induced mechanical and cold allodynia in CB2EGFP reporter mice with established neuropathy. Quantification of the EGFP signal revealed that Langerhans cells were dynamically increased in the epidermis after paclitaxel treatment. Our studies implicate CB2 expressed in previously unrecognized populations of skin cells as a potential target for suppressing chemotherapy-induced neuropathic nociception."

Journal • Preclinical • Oncology • Pain • CCL2 • IL10 • TNFA

Peripherally administered cannabinoid receptor 2 (CBR) agonists lose anti-allodynic effects in TRPV1 knockout mice, while intrathecal administration leads to anti-allodynia and reduced GFAP, CCL2 and TRPV1 expression in the dorsal spinal cord and DRG. (PubMed, Brain Res) - "In rat, intrathecal AM1710 and AM1241 reduced spinal and DRG TRPV1 expression, with CCL2-astrocyte and -microglial co-expression. These data support that CBR agonists can impact spinal and DRG TRPV1 expression critical for anti-allodynia."

Journal • Preclinical • Neuralgia • Pain • CCL2 • GFAP

Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review. (PubMed, IBRO Neurosci Rep) - "Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP."

Journal • Review • Human Immunodeficiency Virus • Immunology • Infectious Disease • Neuralgia • Pain • Peripheral Neuropathic Pain

Peripheral versus central mechanisms of the cannabinoid type 2 receptor agonist AM1710 in a mouse model of neuropathic pain. (PubMed, Brain Behav) - "We conclude that CB R is dispensable for either peripheral or central anti-allodynic actions of AM1710 in neuropathic mice. Cannabinoid CB R agonists produce heightened spinal IL-10 which may be clinically relevant to successfully treat neuropathic pain."

Journal • Preclinical • Neuralgia • Pain • Peripheral Neuropathic Pain • IL10 • TNFA