Serotonin agonists

Serotonin agonists G-protein coupled 5-HT receptors 5-HT3 ion channels cAMP (5-HT-,) t cAMP (5-HT4 7) t PLC (5-HT2) l Release of excitatory neuropeptides l Neurogenic inflammation f vasoconstriction Myocardial infarction, stroke, peripheral vascular occlusion... 

We have not explored all of the dose-response relationships. And with respect to the nature of the cue, we have studies underway now with a variety of serotonin agonists and antagonists, for example, fluoxetine. And have looked at MDMA. We eannot bloek the cue with fluoxetine. We are also looking at 8-hydroxy-DPAT, buspirone. PCPA pretreatment is on the way. So there are a variety of manipulations that we have in process. 

Glennon, R.A. Site-selective serotonin agonists as discriminative stimuli. 

COMMENT I am not sure the serotonin is inhibitory and dopamine excitatory is all that naive. There were clinical studies published where they showed that serotonin agonists could completely suppress the CNS stimulant effects of amphetamine clinically in humans. So you may be seeing the same thing. I am not sure that it has to be a psychedelic activity superimposed. It may simply be some kind of a synergistic attenuation. 

Spampinato, U., Espisito, E., and Samainin, R., Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact, J. Neurochem., 45, 980, 1985. 

Munzar, P., Laufert, M.D., Kutkat, S.W., Novakova, J., Goldberg, S.R. Effects of various serotonin agonists, antagonists, and uptake inhibitors on the discriminative stimulus effects of methamphetamine in rats. J. Pharmacol. Exp. Ther. 291 239, 1999. 

The synthetic applications of this reagent to the synthesis of nitroalkenes have been known since the 1960s.60 Nitration of alkenes with nitryl iodide, generated in situ from iodine and silver nitrite, is convenient for the synthesis of P-nitrostyrenes with various functional groups.61 This method is applied to the synthesis of ortho-methoxylated phenylisopropylamines, which are potent serotonine agonists (Eq. 2.31).62... 

Histamine-receptor Antagonists Serotonin agonists Serotonin antagonists Ergot alkaloids... 

Stewart, M. R., Campbell, A., Sperk, G., and Baldessarini, R. J. (1979) Receptor mechanisms in increased sensitivity to serotonin agonists after dihydroxytryptamine shown by electronic monitoring of muscle twitches in the rat. Psychopharmacology, 60 281-289. 

The tetralins 18a and 18b were potent serotonin agonists in dog vascular smooth muscle (33) but did not elicit hallucinogen-like action in a conditioned avoidance response model in rats (156). However, 18b is a potent pyretic agent in rabbits and produces a rage response in cats (166). Addition of a double bond into the 3,4-position of the tetralins led to decreased serotonin-like action... 

Glennon, R.A. (1992) Concepts for the design of 5-HTiA serotonin agonists and antagonists. Drug Development Research, 26, 251-274. 

Listing of antidepressants grouped by principal mechanism of action in the synapse. Abbreviations MAOI—irreversible = irreversible monoamine oxidase inhibitor MAOI—reversible = reversible monoamine oxidase inhibitor NDRl = norepinephrine/ dopamine reuptake inhibitor NRI = norepinephrine reuptake inhibitor NSRl = norepinephrine/serotonin reuptake inhibitor NSSA = norepinephrine/specific serotonin agonist SRI = serotonin reuptake inhibitor SRl/serotonin-2 blocker = serotonin reuptake inhibitor and serotonin-2 receptor antagonist. 

Sumatriptan is a 5HT (serotonin) agonist indicated in the treatment of migraine. Sumatriptan causes vasoconstriction and must therefore be used with caution in patients with coronary heart disease, such as angina. Concurrent administration of the agonist, sumatriptan and antagonists, such as fluoxetine, which is a selective serotonin re-uptake inhibitor, leads to increased CNS toxicity. 

The opioid analgesics, such os codeine, tramadol and fentanyl may cause drowsiness. Sumatriptan, which is a serotonin agonist, also tends to cause drowsiness. Modern non-steroidal anti-inflammatory drugs, such as diclofenac, do not cause drowsiness. 

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