Serotonin antagonistic effects

In 1954, i.e. about 2 years after the discovery of chlorpromazine in Europe, two American biochemists (Woolley and Shaw) published the hypothesis that schizophrenia and similar psychoses could be based on a disturbance of serotoninergic neurotransmission in the brain. This hypothesis was supported by some facts that had become known shortly beforehand the spectacular psychotropic actions of LSD (lysergic acid diethylamide), which can trigger disturbances in perception, thought and feelings as well as hallucinations in healthy subjects (Stoll, 1947) and the serotonin-antagonistic effects of LSD, i.e. its ability to block the actions of serotonin in various pharmacological tests. 

B. Specific drugs and antidotes. For suspected serotonin syndrome, anecdotal reports claim benefit from cyproheptadine (Periactin), 4 mg orally every hour for 3 doses, or methysergide (Sansert), 2 mg orally every 6 hours for 3 doses, presumably because of the serotonin antagonist effects of these drugs. 

The alleged interaction between the MAOIs and antihistamines appears to be based on a single animal study, and is probably more theoretical than real The exception seems to be cyproheptadine, which can reduce the effect of MAOIs because of its serotonin antagonist effect, see MAOIs or RIMAs + Antihistamines Cyproheptadine , below. 

Two general classes of alkaloids are distinguished in ergot amine alkaloids and amino acid alkaloids (table 5.9) (Peroutka 1996). While the amine alkaloids are selective for antagonist effects on serotonin receptors, the amino acid alkaloids are less selective and act upon other monoamine receptors. The constituents of interest for cognitive enhancement are predominantly the amine alkaloids. 

Agonist/antagonist effects on serotonin receptors Time-dependent increases/decreases on dopamine and norepinephrine Age-dependent effects on MAO Increased firing of locus coeruleus neurons... 

Uses Allergic Rxns itching Action Phenothiazine antihistamine serotonin antagonist Dose Adults. 4-20 mg PO qSh max 0.5 mg/kg/d Feds. 2-6 y 2 mg bid-tid (max 12 mg/24 h) 7-14 y 4 mg bid-tid in hepatic impair Caution [B, ] BPH Contra Neonates or <2 y NAG BOO acute asthma GI obst Disp Tabs, syrup SE Anticholinergic, drowsiness Interactions T Effects Wf CNS depressants, MAOIs, EtOH X effects OF epi, fluoxetine EMS Use other CNS depressants w/ caution concurrent EtOH use can T CNS depression higher epi doses may be needed if used OD May cause mood changes, Szs, CNS depression, or CNS stimulation symptomatic and supportive... 

The serotonin antagonist ondansetron (Zofran) has proved effective in the prevention of nausea and vomiting due to chemotherapy. 

Mechanism of Action An ergotamine derivative and alpha-adrenergicblocker that directly stimulates vascular smooth muscle, resulting in peripheral and cerebral vasoconstriction. May also have antagonist effects on serotonin. Therapeutic Effect Suppresses vascular headaches. 

In addition to their effects on norepinephrine and serotonin, TCAs have significant antagonistic effects at muscarinic and histaminic receptors. While TCAs appear to bind equally to all subtypes of the muscarinic receptor, they show preferential affinity for the histaminic Hi receptor over the Hi receptor subtype. The... 

Denoble VJ, Schrack LM, Reigel AL, et al Visual recognition in squirrel monkeys effects of serotonin antagonists on baseline and hypoxia induced performance deficits. Pharmacol Biochem Behav 39 991-996, 1991 Depue RA, Karuss SP, Spoont MR A two-dimensional threshold model of seasonal bipolar affective disorder, in Psychopathology An Interactional Perspective. Edited by Magnusson D, Ohman A. Orlando, FL, Academic Press, 1987, pp 95-123... 

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