Serotonin antagonists mechanisms/effects

The exact mechanism of mescaline has not been clearly defined. The central nervous system effects of mescaline appear to involve stimulation of both serotonin and dopamine receptors. In experimental studies, these effects can be blocked by either serotonin antagonists such as methysergide or dopamine antagonists such as haloperidol. Mescaline is structurally related to the amphetamines and cathine (khat). Sympathomimetic effects can occur and are thought to be centrally mediated. Mescaline does not appear to inhibit monoamine oxidase. 

Although the mechanism is not fully understood, it has been suggested that because cyproheptadine is a serotonin antagonist it blocks or opposes the serotonergic effects of these SSRIs. 

Koella has reviewed the evidence implicating the involvement of serotonin in the sleep-wake cycle but the involvement of specific serotonin receptor subtypes in sleep mechanisms is unclear. Experimental evidence suggests that 5-HTia agonists delay the onset of REM sleep while 5-HT2 antagonists suppress REM and have variable effects on non-REM sleep. 

The mechanism of action of neuroleptics is not sufficiently clear. However, it is believed that they are antagonists of dopamine and dopaminomimetics, and that their effect is connected in some way with the blockage of dopamine D receptors, which results in changes of behavioral reactions. Moreover, it is possible that they also block action on the serotonin receptors and M-choline receptors. It also is possible that antipsychotic agents disrupt the process of the release and return neuronal uptake of a number of biogenic amines. 

Mechanism of Action An antipsychotic agent that provides partial agonist activity at dopamine and serotonin (S-HTj ) receptors and antagonist activity at serotonin (5-HTja) receptors. Therapeutic Effect Diminishes schizophrenic behavior. Pharmacokinetics Well absorbed through the GI tract. Protein binding 99% (primarily albumin). Reaches steady levels in 2 wk. Metabolized in the liver. Eliminated primarily in feces and, to a lesser extent, in urine. Not removed by hemodialysis. Half-life 75 hr. 

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. 

Phentolamine is a potent competitive antagonist at both K and k2 receptors (Table 10-1). Phentolamine reduces peripheral resistance through blockade of K receptors and possibly k2 receptors on vascular smooth muscle. Its cardiac stimulation is due to antagonism of presynaptic k2 receptors (leading to enhanced release of norepinephrine from sympathetic nerves) and sympathetic activation from baroreflex mechanisms. Phentolamine also has minor inhibitory effects at serotonin receptors and agonist effects at muscarinic and Hi and H2 histamine receptors. Phentolamine s principal adverse effects are related to cardiac stimulation, which may cause severe tachycardia, arrhythmias, and myocardial ischemia. Phentolamine has been used in the treatment of pheochromocytoma. Unfortunately oral and intravenous formulations of phentolamine are no longer consistently available in the United States. 

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