Letter to the Editor - SAGE Journals

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Crockard HA, Allen K, Avery S, Ross-Russell RW (1983) Ce rebral protective properties of the commercial vehicle so lution of naloxone. Lancet 2: 1143.
Journal of Cerebral Blood Flow and Metabolism 4:308 © 1984 Raven Press, New York

Letter to the Editor

The authors reply:

To the Editor: Brandt et aI. (1983) have reported that the preservative parabens contained in com­

To the Editor: Our study reported that pure nal­

mercial naloxone preparations cause a dose-depen­

oxone does not relax human pial cortical arteries in

dent relaxation of human pial cortical arteries fol­

vitro but that the Nalonee® (Narcan®) preparation

lowing contractions caused by a variety of sub­

does. Nalonee (Narcan) contains both naloxone and

stances,

the preservatives methyl-

including potassium, serotonin, and

and

propylparaben

which, we showed, do relax cerebral arteries. Re­

hemorrhagic cerebrospinal fluid. Although not stated as such, the authors appear to suggest that

ports on the effects of any drug including naloxone

reported beneficial effects of naloxone in both clin­

should state both its source and the addition of any

ical and experimental stroke may be due to the pres­

preservatives or solvents. It is to be regretted that

ence of the parabens. Eight of 13 experimental

such data have not always been provided in reports

studies reported to date have demonstrated a ben­

on the cerebrovascular effects of naloxone. We

eficial effect for naloxone at doses in the range of

view our article as a cautionary tale. We were

2.0-7.0 mg/kg (Faden, 1983). The majority of these

careful not to suggest, implicitly or otherwise, that

experimental studies have employed naloxone hy­

the controversy over whether naloxone has any

drochloride (supplied by Endo Laboratories) as a

beneficial effect in a variety of cerebrovascular

powder without preservatives and have adminis­

preparations would be resolved simply by knowing

tered the drug in physiological saline. The mecha­

whether parabens were present or not. However,

nism by which naloxone exerts it therapeutic effects

following our article, Crockard et al. (1983) have

in stroke or spinal injury remains speculative. How­

reported briefly that, in a gerbil preparation of ce­

ever, we have shown that this opiate antagonist im­

rebral ischemia, "the most active solution in terms

proves spinal cord blood flow after traumatic cer­

of CBF and possibly also in cerebral protection is

vical injury in the cat (Faden et aI., 1981) and im­

the vehicle solution and not the naloxone dissolved

proves local blood flow after ischemic cerebral

in it." Whatever the cerebrovascular merits of pure

injury in the dog (Faden et aI., 1982). In addition,

naloxone prove to be, the parabens themselves are

the beneficial effects of naloxone in neurological

worthy of further study.

outcome after ischemic spinal injury are duplicated by other opiate antagonists (not prepared with par­ abens), such as WIN44,441-3; moreover, these ef­

Lennart Brandt

fects are dose-related and stereospecific, pointing

Karl-Erik Andersson

to an opiate receptor-mediated mechanism of ac­

Bengt Hindfelt

tion (A. I. Faden, unpublished observations).

Bengt Ljunggren John D. Pickard

Alan I. Faden

Departments of Neurosurgery

Neurobiology Research Unit

and Clinical Pharmacology

Uniformed Services University

University Hospital of Lund, Sweden

of the Health Sciences

and Department of Neurosurgery

Bethesda, Maryland, U.S.A.

Southampton General Hospital, England

References Reference

Brandt L, Andersson K-E, Hindfelt B, Ljunggren B, P ickard JD

(1983) Are the vascular effects of naloxone attributable to

Crockard HA, Allen K, Avery S, Ross-Russell RW

the preservatives methyl- and propylparaben? J Cereh Blood

(1983) Ce­

rebral protective properties of the commercial vehicle so­

Flow Metahol 3:395-398 Faden AI (1983) Opiate antagonists in the treatment of stroke. Curr Concepts Cerehrovasc Dis 18:27-31 Faden AI, Jacobs TP, Holaday JW (1981) Endorphins in exper­ imental spinal injury: therapeutic effect of naloxone. Ann Neural 10:326-332 Faden AI, Hallenbeck JM, Brown CQ (1982) Treatment of ex­ perimental stroke: comparison of naloxone and thyrotropin­ releasing hormone. Neurology 32:1083-1087

lution of naloxone. Lancet

308

2:1143