1. Agents for Serotonergic Neurotransmission Inhibitors of serotonin storage –Amphetamine, methylphenidate, modafinil –Fenfluramine, dexfenfluramine –Methylenedioxymethamphetamine (MDMA, “ecstasy”) Inhibitors of serotonin degradation –MOAI, RIMA Reuptake inhibitors –TCAs: NET and SERT blocker with anticholinergic, antiadrenergic and antihistaminergic action –SSRIs: fluoxetine, citalopram, fluvoxamine, paroxetine, sertraline, escitalopram –SNRIs: venlafaxine, duloxetine Atypical antidepressants –Bupropion, mirtazapine: 5HT 2A/2C R and alpha2 R blocker, nefazodone: 5HT 2 R blocker, trazodone: 5HT 2 R blocker Serotonin receptor agonists Serotonin receptor antagonists

2. Serotonin receptor agonists Ergots from the rye rust fungus Clasviceps purpurea: 5HTRs agonists –intense vasoconstriction -> ergotism: necrosis and gangrene Lysergic acid diethylamide (LSD), a semisynthetic ergot: 5HT Rs agonist –hallucinations and sensory dysfunction Buspirone: 5HT 1A R agonist –to treat anxiety and migraine headache Triptans - sumatriptan, riztriptan, almotriptan, frovatriptan, eletriptan, zolmitriptan: 5HT 1B/1D R agonists –to treat migraine headache Trazodone  meta-chlorophenylpiperazine (mCPP): 5HT 2A/2C R agonist –to treat depression and insomnia Cisapride: 5HT 4 R agonist –GI motility

3. Serotonin receptor antagonists Ketanserin: 5HT 2A/2C R antagonist with alpha- adrenergic activity –topical; in glaucoma Ondansetron: 5HT 3 R antagonist; chemo-trigger zone –antiemetic Alosetron: 5HT 3 R antagonist –use for diarrhea associated with IBS Tegaserod, prucalopride: 5HT 4 R antagonist –to treat constipation associated with irritable bowel syndrome (IBS)

4. Mediat or ActionObject Cholinerg ic Adrener gic GABAer gic Glutamatergi c Dopamine rgic Serotonergic Chann el ?Ligand 5HT3 Chann el openingCl- A Chann el openingNa+,K+NM, NN AMPA,Kainat e Chann el openingNa+,K+,Ca+ NMDA GiinhibitionAC: cAMPM2alpha2BmGlu II,IIID2,3,4 5HT1A,B,D,E, F GoopeningK+ (GIRK)M2alpha2B Gq stimulatio n PLC: IP3/DA G M1,M3,M 5 alpha1 mGlu ID1,55HT2A,B,C Gs stimulatio n AC: cAMP beta1,2, 3 D1,55HT4,6,7