(-)-10-(3-[Dimethylamino]-2-methylpropyl)-2-methoxy-phenothiazine maleate salt

Absorption

Methotrimeprazine has an incomplete oral bioavailability, because it undergoes considerable first-pass-metabolism in the liver. Oral bioavailability is approximately 50 to 60%.

Toxicity

Symptoms of overdose include convulsions, spastic movements, and coma.

Originator

Levoprome ,Lederle,US,1966

The Uses of (-)-10-(3-[Dimethylamino]-2-methylpropyl)-2-methoxy-phenothiazine maleate salt

Analgesic

The Uses of (-)-10-(3-[Dimethylamino]-2-methylpropyl)-2-methoxy-phenothiazine maleate salt

(R)-Methotrimeprazine acts as an analgesic agent.

Background

A phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)

Indications

For the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder.

Definition

ChEBI: A member of the class of phenothiazines that is 10H-phenothiazine substituted by a (2R)-3-(dimethylamino)-2-methylpropyl group and a methoxy group at positions 10 and 2 respectively.

Manufacturing Process

95% sodamide (2.33 g) is added to a boiling solution of 3- methoxyphenthiazine (12 g) in anhydrous xylene (150 cc) and the mixture is heated with agitation under reflux for 1? hours. A solution of 1- dimethylamino-2-methyl-3-chloropropane (8.2 g) in anhydrous xylene (90 cc) is then run in over a period of 45 minutes while the reaction temperature is maintained and heating under reflux is continued for 18 hours.
After cooling, the reaction mixture is agitated with a mixture of water (40 cc) and a normal solution of methanesulfonic acid (70 cc), the xylene layer is removed and the acid liquors are washed with ether (200 cc). The aqueous phase is then made alkaline with sodium hydroxide (d = 1.33; 10 cc) and the liberated base is extracted with ether. The ethereal solution is dried over anhydrous potassium carbonate and concentrated at normal pressure. On distillation of the residue under reduced pressure 3-(3-methoxy-10- phenthiazinyl)-2-methyl-1-dimethylaminopropane (11.3 g) is obtained, MP 103°C, BP 182° to 191°C/0.15 mm Hg. The hydrochloride prepared in isopropanol melts at about 90°C.

brand name

Levoprome (Immunex).

Therapeutic Function

Analgesic

Pharmacokinetics

Methotrimeprazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)

Metabolism

Hepatic. Methotrimeprazine is metabolized in the liver and degraded to a sulfoxid-, a glucuronid- and a demethyl-moiety.