I N D U S T R Y & B U S I N E S S

Spotlight Turns on Tranquilizers While Wyeth launches new compound, meprobamate dropped from pharmacopeia, phenothiazines eyed for dangers

A trio of events has put a spotlight on tranquilizers. Meprobamate does not appear in the new edition of the U.S. Pharmacopeia; phenothiazines are be­ing considered a possible cause of cat­aracts; and Wyeth has released infor­mation on oxazepam—first of the com­pany's new series of intermediate tranquilizers up for a new drug ap­proval (NDA) from the Food and Drug Administration.

Meprobamate, one of the most widely used tranquilizers in the U.S., will not be listed in the forthcoming edition of the USP because of doubts of USP consultants about its therapeu­tic value as a tranquilizer. Comment­ing on the USP action, Dr. Frank M. Berger, president of Wallace Labora­tories and developer of meprobamate, calls attention to the fact that mepro­bamate has been used widely and ef­fectively for more than 10 years. Wallace Laboratories division of Car­ter Products, Inc., markets the drug under the trade name Miltown. The drug is also sold by Wyeth (trade name Equanil) and by 17 other com­panies under its generic name.

Groups. The major tranquilizers used in the U.S. may be divided into three groups: the rauwolfia deriva­tives, the phenothiazines, and the thio-xanthenes. The phenothiazines are the most widely used in both psychi­atry and general medicine. The phe­nothiazines are usually divided into three groups based on the chemical structure of the side chain. The side chain can be a piperazine group, a piperidine group, or a chlorpiOmazine model group (characterized by a C 3

straight side chain). The phenothia-zine derivatives accounted for about one third of the total sales of tranquil­izers last year—a market which totals about $220 million.

Anxiety over phenothiazines as a possible cause of cataracts was gen­erated by a statement made by Dr. John Saunders, a research worker at Rockland State Hospital (Rockland, N.Y.). A clarifying statement was re-

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leased later by Dr. Joseph Barsa, su­pervising psychiatrist at the hospital.

It is true, Dr. Barsa says, that 178 patients out of 658 female patients ex­amined demonstrated opacities of either the lens alone or of the lens and cornea. These opacities, he adds, are different in appearance and nature from ordinary cataracts and no visual impairment was detected. Although all the patients showing these changes had been on various phenothiazine derivatives, he continues, a true causal relationship between the phenothia­zine drugs and the ocular opacities is not yet established and must await further investigation.

Not New. Phenothiazine manufac­turers received the Rockland State Hospital report of side effects calmly. Occurrence of ocular opacities in pa­tients who use phenothiazines is not new, they note, and has been reported several times previously. None of the cases reported to date in the U.S., he says, have involved a visual impair­ment which can be directly attributed to the use of phenothiazines. There are, however, one or two reports of patients with diminished visual ocuity now under investigation.

Studies of patients on phenothia-

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zine have indicated that dosage, dura­tion of therapy, and exposure to light are important factors in determining the type and amount of any side ef­fects. In general, the larger the dose and the longer the duration of therapy and the greater the exposure to light, the greater is the possibility of a side effect such as opacity.

First to detect and report these

26 C&EN MAY 3, 1965