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