Hodgkinsine is a pyrrolidinoindoline alkaloid that has been found inP. colorataand has analgesic activity.1It increases latency to paw licking in the hot plate test and latency to tail withdrawal in the tail-flick test in mice when administered at a dose of 5 mg kg. 1.Amador, T.A., Verotta, L., Nunes, D.S., et al.Antinociceptive profile of hodgkinsinePlanta Med.66(8)770-772(2000)
Deltorphin II is a peptide agonist of δ2-opioid receptors.1,2It is selective for δ-opioid receptors over μ- and κ-opioid receptors in radioligand bindings assays (Kis = 0.0033, >1, and >1 μM, respectively) and induces [35S]GTPγS binding in mouse brain membrane preparations (EC50= 0.034 μM). Deltorphin II (0.12 mg kg) decreases the infarction zone:risk zone ratio in a rat model of myocardial ischemia-reperfusion injury induced by coronary occlusion, an effect that can be reversed by the δ2-opioid receptor antagonist naltriben but not the δ1-opioid receptor antagonist BNTX.3Intrathecal administration of deltorphin II (15 μg animal) increases latency to withdraw in the paw pressure and tail-flick tests in rats.4 1.Raynor, K., Kong, H., Chen, Y., et al.Pharmacological characterization of the cloned κ-, δ-, and μ-opioid receptorsMol. Pharm.45(2)330-334(1994) 2.Scherrer, G., Befort, K., Contet, C., et al.The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: A parallel study of mu, delta and combinatorial opioid receptor knockout miceEur. J. Neurosci.19(8)2239-2248(2004) 3.Maslov, L.N., Barzakh, E.I., Krylatov, A.V., et al.Opioid peptide deltorphin II simulates the cardioprotective effect of ischemic preconditioning: role of δ2-opioid receptors, protein kinase C, and KATP channelsBull. Exp. Biol. Med.149(5)591-593(2010) 4.Labuz, D., Toth, G., Machelska, H., et al.Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin II in rat spinal cord: A search for selectivity of delta receptor subtypesNeuropeptides32(6)511-517(1998)
Hodgkinsine B is an alkaloid and isomer of hodgkinsine that has analgesic activity.1It increases the latency to tail withdrawal in the tail-flick test in mice when administered at a dose of 10 mg kg. 1.Kodanko, J.J., Hiebert, S., Peterson, E.A., et al.Synthesis of all low-energy stereoisomers of the tris(pyrrolidinoindoline) alkaloid hodgkinsine and preliminary assessment of their antinociceptive activityJ. Org. Chem.72(21)7909-7914(2007)
Mambalgin 1 TFA, a selective inhibitor of ASIC1a (with IC50 values of 192 nM for human ASIC1a and 72 nM for the ASIC1a 1b dimer), preferentially binds to the channel in its closed inactive state. It demonstrates selectivity for ASIC1a over a range of other channels, including ASIC2a, ASIC3, TRPV1, P2X2, 5-HT3, Nav1.8, Cav3.2, and Kv1.2. In vivo, Mambalgin 1 TFA effectively prolongs the latency of the withdrawal response in mouse tail-flick and paw-flick tests.
β-Endorphin (1-27) is an endogenous peptide that binds to μ-, δ-, and κ-opioid receptors (Kis = 5.31, 6.17, and 39.82 nM, respectively, in COS-1 cells expressing rat receptors). It binds to rat and mouse brain membrane preparations (IC50s = 1.1 and 5.7 nM, respectively) and induces chemotaxis of human monocytes in vitro when used at a concentration of 1 nM. Intracerebroventricular administration of β-endorphin (1-27) increases the latency to tail withdrawal in response to thermal stimulation in mice with a median antinociceptive dose (AD50) of 1,500 pmol per animal. It inhibits antinociception induced by β-endorphin in mice in response to thermal stimuli when administered at a dose of 65 pmol per animal. In rats, β-endorphin (1-27) does not affect drug-associated place preference when administered at doses up to 20 μg, i.c.v., but inhibits β-endorphin-induced place preference when administered at a dose of 10 μg per animal.
Salvinorin A propionate is a selective partial agonist at κ1-opioid receptors (KOR) with a Ki value of 32.6 nM. It inhibits adenylate cyclase (EC50 = 4.7 nM) in HEK293 cells transfected with human KOR. It is selective for KORs over μ, δ, and ORL-1 opioid receptors and has no effect at serotonin, dopamine, muscarinic, or adrenergic receptors. In mice, salvinorin A propionate (13 μg, i.c.v.) reduces nociceptive responses in a radiant heat tail-flick assay, though not as potently as salvinorin A .
SRA880 is a non-peptide somatostatin sst(1) receptor antagonist which displays a significantly lower affinity for the other human recombinant somatostatin receptors ( pK(d)= 6.0) or a wide range of neurotransmitter receptors, except for the human dopamine
τ-Fluvalinate is a pyrethroid acaricide.1It induces tail currents in Western honeybee (A. mellifera) voltage-gated sodium channels (AmNav1) expressed inXenopusoocytes (EC50= 60 nM). It also induces tail currents in honeybee parasitic Varroa mite (V. destructor) Nav1 channels (VdNav1) expressed inXenopusoocytes (EC50= 160 nM) with a faster tail current decay than that of AmNav1 channels. Topical application of τ-fluvalinate (2 μl) in combination with coumaphos , atrazine , 2,4-DMPF, chlorpyrifos , and chlorothalonil does not affect honeybee queen mass, egg-laying patterns, or the mass of daughter worker bees at emergence.2Formulations containing τ-fluvalinate have been used to control Varroa mites in beehives. 1.Gosselin-Badaroudine, P., and Chahine, M.Biophysical characterization of the Varroa destructor NaV1 sodium channel and its affinity for τ-fluvalinate insecticideFASEB J.31(7)3066-3071(2017) 2.McAfee, A.Honey bee queen health is unaffected by contact exposure to pesticides commonly found in beeswaxSci. Rep.11(1)15151(2021)
DB293 is an inhibitor of PIT-1 and BRN-3 transcription factors. DB293 binds as head-to-tail stacked dimers in the minor groove of 5'-ATGA sequence, thereby leading to an increase in the size of minor groove.