bemesetron and 4-iodo-2-5-dimethoxyphenylisopropylamine

We used the formalin test to clarify the 5-hydroxytryptamine (5-HT) receptor subtypes involved in the modulation of spinal nociceptive transmission in rats. Intrathecal administration of a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetraline (8-OH-DPAT; 1, 10, and 30 microg), or a 5-HT1B receptor agonist, 1, 4-dihydro-3-(1, 2, 3, 6-tetrahydro-4-pyridinyl)-5H-pyrrol (3, 2-b) pyridin-5-one (CP 93129; 1 and 10 microg), produced no significant change in the number of flinches. A 5-HT(2) receptor agonist, (+/-)-2, 5-dimethoxy-4-iodoamphetamine (DOI; 10, 30, and 100 microg), and a 5-HT3 receptor agonist, 2-methyl-5-HT (100 and 300 microg), produced dose-dependent decreases in the number of flinches in phases 1 (1 to 6 min) and 2 (10 to 61 min) of the test. The antinociceptive effects of DOI and 2-methyl-5-HT were antagonized by intrathecal pretreatment with a 5-HT2 receptor antagonist, ketanserin, and a 5-HT3 receptor antagonist, 3-tropanyl-3, 5-dichlorobenzoate (MDL-72222), respectively. These results suggest that 5-HT2 and 5-HT3 receptors in the spinal cord mediate antinociception to chemical stimuli.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Animals; Dose-Response Relationship, Drug; Formaldehyde; Injections, Spinal; Male; Nociceptors; Pain; Pain Measurement; Pyridines; Pyrroles; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Spinal Cord; Synaptic Transmission; Tropanes

The effect of serotonin 5-HT2 receptor stimulation on long-term potentiation (LTP) in the primary visual cortex was investigated by using rat brain slices in vitro. Field potentials evoked by stimulation of layer IV were recorded in layer II/III. The 5-HT2 receptor agonist 1-(2,5-dimethyl-4-iodophenyl)-2-aminopropane (DOI) did not affect baseline synaptic potentials evoked by single-pulse test stimulation, but significantly inhibited the induction of LTP in a concentration-dependent manner (0.1-10 microM). The LTP-inhibiting effect of DOI (10 microM) was blocked by the 5-HT2,7 receptor antagonist ritanserin (10 microM), but not by the 5-HT1A receptor antagonist NAN-190 (10 microM) nor by the 5-HT3,4 receptor antagonist MDL72222 (10 microM). The inhibitory effect of DOI was also blocked by the phospholipase C inhibitor U73122, but not by its inactive analogue U73343. These results suggest that visual cortex LTP is inhibited by activation of the 5-HT2 receptor-phospholipase C system. In addition, the LTP-inhibiting effect of DOI was abolished by the presence of the GABAA receptor antagonist bicuculline (10 microM), suggesting that 5-HT2 receptor-mediated inhibition of visual cortex LTP is dependent on GABAergic inhibition.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Animals; Bicuculline; Electrophysiology; Estrenes; GABA Antagonists; gamma-Aminobutyric Acid; In Vitro Techniques; Long-Term Potentiation; Male; Phosphodiesterase Inhibitors; Piperazines; Pyrrolidinones; Rats; Rats, Wistar; Receptors, GABA-A; Receptors, Serotonin; Ritanserin; Serotonin Antagonists; Serotonin Receptor Agonists; Tropanes; Type C Phospholipases; Visual Cortex

The effects of 5-hydroxytryptamine on the membrane potential and input resistance of 86 dorsal horn neurons were studied using intracellular recordings in isolated, hemisected spinal cords of adult frogs (Rana pipiens). Bath application of serotonin (5-100 microM) caused membrane depolarizations in 58 (67%) neurons, hyperpolarizations in 12 (14%) cells, biphasic responses in nine (11%) neurons, and no detectable change in seven (8%) cells. In some neurons depolarized by serotonin, the amine's responses could be mimicked by the selective 5-HT2 agonist (+/-)-1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride and the 5-HT1C/2 agonist alpha-methyl-5-hydroxytryptamine, and blocked by the 5-HT1C/2 antagonists ketanserin and mianserin. In other neurons depolarized by serotonin, the 5-HT3 agonist 2-methyl-5-hydroxytryptamine mimicked, and the 5-HT3 antagonist, 3-tropanyl-3,5-dichlorobenzoate, blocked the serotonin-induced responses. Depolarizing responses due to activation of 5-HT1C/2 receptors were generally accompanied by increases in the membrane input resistance, whereas depolarizations mediated by 5-HT3 receptors were associated with a decreased membrane input resistance. Superfusion with tetrodotoxin or low-Ca2+/high-Mg(2+)-containing media abolished about half of the depolarizing responses. Hyperpolarizations caused by serotonin were associated with a decrease in membrane input resistance, and might have been due to activation of a potassium conductance. These responses persisted in bathing solutions containing tetrodotoxin or low-Ca2+/high-Mg2+. The 5-HT1A agonist 8-hydroxy-2-(di-N-propylamine)tetralin hydrobromide mimicked, whereas the 5-HT1A antagonist spiroxatrine blocked, these hyperpolarizing responses. Other antagonists selective for 5-HT1C/2 or 5-HT3 receptors were without effect. Serotonin-produced biphasic responses consisted of either an initial depolarization followed by a hyperpolarization or the reverse. The selective 5-HT2 agonist (+/-)-1(2,5-dimethyoxy-4-iodophenyl)-2-aminopropane hydrochloride could only mimic the depolarizations, whereas the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamine)tetralin hydrobromide produced only the hyperpolarizations. Spiroxatrine, a 5-HT1A antagonist, blocked only the hyperpolarizations without affecting the depolarizations, and methysergide, a non-specific 5-HT receptor antagonist, depressed both the depolarizations and hyperpolarizations. Serotonin also appeared to affect spinal dorsal horn neurons in

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Animals; Dioxanes; Electric Stimulation; Evoked Potentials; Female; In Vitro Techniques; Ketanserin; Kinetics; Male; Membrane Potentials; Methysergide; Mianserin; Neurons; Rana pipiens; Serotonin; Serotonin Antagonists; Spinal Cord; Spiro Compounds; Synapses; Tetrodotoxin; Tropanes