PT  - JOURNAL ARTICLE
AU  - M J Goldberg
AU  - R Spector
AU  - C K Chiang
TI  - Transport of diphenhydramine in the central nervous system.
DP  - 1987 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 717--722
VI  - 240
IP  - 3
4099  - http://jpet.aspetjournals.org/content/240/3/717.short
4100  - http://jpet.aspetjournals.org/content/240/3/717.full
SO  - J Pharmacol Exp Ther1987 Mar 01; 240
AB  - The transport and metabolism of diphenhydramine was studied in vitro in the isolated rabbit choroid plexus and in vivo in New Zealand white rabbits and Sprague-Dawley rats. In vitro, [14C] diphenhydramine was accumulated by a saturable, energy-requiring system in choroid plexus. In vivo, 20 min after intraventricular injection into rabbits, [14C]diphenhydramine was cleared from cerebrospinal fluid much more rapidly than [3H]sucrose, a molecule transported in the central nervous system by simple diffusion. In vivo, employing the in situ rat brain perfusion technique, [14C]diphenhydramine was cleared from the cerebral perfusion fluid as rapidly as [14C]diazepam. However, the clearance of [14C]diphenhydramine, but not [14C]diazepam, was inhibited by the addition of 10 mM unlabeled diphenhydramine to the perfusate. These in vivo and in vitro results show that diphenhydramine, unlike diazepam, is transported between blood, brain and cerebrospinal fluid, in part, by saturable, carrier-mediated transport processes at both the blood-brain and blood-cerebrospinal fluid barriers.