Tryptamine guanosine carbamate

Tryptamine guanosine carbamate (TpGc) is a selective HINT1 (histidine triad nucleotide-binding protein 1) inhibitor (Ki=34 μM, Kd=3.65 μM). Tryptamine guanosine carbamate significantly enhances morphine antinociception while preventing the development of tolerance[1].

Signaling Pathways >> Others >> Others

Research Areas >> Neurological Disease

Pretreatment with 20 nmol TpGc enhanced morphine antinociception in 129 HINT1+/+ mice and is devoid of effect in HINT1-/- mice.The administration of 7 and 20 nmol of TpGc 20min before the morphine priming dose significantly reduces the development of acute antinociceptive tolerance in HINT1+/+ mice but not in HINT1-/- animals[1]. TpGc reduces the recruitment of NMDAR activity promoted by morphine. In mice suffering from chronic constriction injury concurrent with increased NMDAR activity, a single intracerebroventricular administration of TpGc (20 nmol) attenuates NMDAR function and alleviated mechanical allodynia for several days[1].

[1]. Garzón J, et al. HINT1 protein: a new therapeutic target to enhance opioid antinociception and block mechanical allodynia. Neuropharmacology. 2015;89:412-423.