メソリダジン

Based upon animal studies, mesoridazine, as with other phenothiazines, acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. In addition, the phenothiazines exhibit at least part of their activities through depression of hypothalamic centers. Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic blocking action.

Sudden and unexpected deaths have occurred in patients receiving phenothiazines, especially during long-term administration of the drugs. In some patients, sudden death appeared to result from asphyxia (secondary to failure of the cough reflex) or cardiac arrest. /Phenothiazines/

In general, overdosage of phenothiazines may be expected to produce effects that are extensions of common adverse effects; severe extrapyramidal reactions, hypotension, and sedation have been the principal effects reported. CNS depression progressing to coma with areflexia may occur; patients with early or mild intoxication may experience restlessness, confusion, and excitement. Other reported effects associated with acute phenothiazine overdosage have included tachycardia, ECG changes and cardiac arrhythmias, hypothermia, miosis, tremor, muscle twitching, spasm or rigidity, seizures, muscular hypotonia, ileus, dry mouth, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, possibly with sudden apnea. /Phenothiazines/

...THIORIDAZINE SULFOXIDE.../WAS FOUND/ TO HAVE RELATIVELY SLIGHT EFFECT ON RETINAL ENZYMES IN VIVO & NO EVIDENT TOXIC EFFECT ON RETINA IN CATS...

LD50 Rat oral 664 mg/kg

LD50 Mouse oral 560 mg/kg

LD50 Mouse iv 26 mg/kg

LD50 Rabbit oral 7800 mg/kg

LD50 MICE INTRAVENOUS 33 MG/KG /BESYLATE/

LD50 MICE SUBCUTANEOUS 611 MG/KG /BESYLATE/

LD50 MICE ORAL 346 MG/KG /BESYLATE/

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

Well absorbed from the gastrointestinal tract.

TOTAL URINARY & FECAL EXCRETION BY MONKEYS (10 DAY PERIOD) OF THIORIDAZINE WAS 64-76% & 83-92% FOR MESORIDAZINE (FECAL EXCRETION 2-4 TIMES GREATER). GREATER EXCRETION OF LATTER MAY BE DUE TO LESSER OVERALL TISSUE ADSORPTION OR LESS EXTENSIVE ENTERO-HEPATIC CYCLING.

WELL ABSORBED FROM GI TRACT. ONSET & DURATION OF ACTION & METABOLIC FATE... NOT...PRECISELY DETERMINED /HUMAN, ORAL, IM/. IN ANIMAL STUDIES, APPROX 2/3 OF DOSE...EXCRETED IN FECES VIA BILE & 1/3 OF DOSE...EXCRETED IN URINE. /BESYLATE/

PHENOTHIAZINES CROSS PLACENTAL BARRIER & MAY APPEAR IN MILK OF NURSING MOTHERS...PHENOTHIAZINES &...METABOLITES...EXCRETED IN URINE, BILE, & FECES. CERTAIN METABOLITES &...FREE DRUGS...DETECTED IN URINE UP TO 6 MO AFTER THERAPY...DISCONTINUED /HUMAN, ORAL, IM/

PHENOTHIAZINES...ABSORBED WELL FROM GI TRACT & FROM PARENTERAL SITES. GENERALLY...CLEARED FROM PLASMA WITHIN APPROX 3 HR...DISTRIBUTED TO MOST BODY TISSUES...HIGH CONCN OF UNCHANGED DRUG...IN BRAIN...METABOLITES PREDOMINATE IN LUNG, LIVER, KIDNEYS...SPLEEN /HUMAN, ORAL, IM/