PRL 8 53

Psychopharmacology 56, 249-253 (1978) Psychopharmacology
9 by Springer-Verlag 1978
PRL-8-53"
Enhanced Learning and Subsequent Retention in Humans
as a Result of Low Oral Doses of New Psychotropic Agent
NIKOLAUS R. HANSL and BEVERLEY T. MEAD
Department of Medicinal Chemistry and Department of Psychiatry, Creighton University, Omaha, Nebraska 68178, U.S.A.
Abstract. The effect of 3-(2-benzylmethylaminoethyl) intellectual performance. It seems to be necessary for

benzoic acid methyl ester hydrochloride (PRL-8-53) optimal functioning to have an optimal balance of
on learning and on retention of verbal information in activity of all agonists and conductive systems con-
human subjects was investigated. Using the serial cerned. This balance may vary from species to species.
anticipation method under double-blind conditions While in the rat a cholinergic increase may be required
it was found that PRL-8-53 causes slight improvement for optimal performance (Rech, 1968), the opposite
of acquisition. Retention of verbal information was may be true for man (Boshes, 1970). A reduction of
found improved to a statistically significant degree serotonergic activity seems to benefit the experimental
(most P values better than 0.01, some better than animal (Tenen, 1967; Schlesinger et al., 1968). An
0.001). No significant changes were found for either increase in dopaminergic activity appears to be bene-
visual reaction time or motor control after drug when ficial in man, or at least in the Parkinson patient
compared with placebo values. (Boshes, 1970).
This paper reports the results obtained with a
Key words: Learning - Memory - Benzoic acid
novel monoamine, identified as 3-(2-benzylmethyl-
derivatives - Phenethylamines
amino ethyl) benzoic acid methyl ester hydrochloride
(PRL-8-53). The chemistry of this and related com-
pounds is described in detail elsewhere (Hoffmann-
La Roche, 1973; Hansl, 1974a). The compound is a
Early findings related to drug-induced facilitation of benzoic acid derivative containing within its structure
learning and memory have been reviewed by Mc- the phenethylamine skeleton. It also meets structural
Gaugh and Petrinovich (1965). New studies and new criteria required for interaction with cholinergic
compounds are being reported continuously (Wolt- receptors. PRL-8-53 has produced a cholinergic re-
huis, 1971). The role of RNA and protein synthesis sponse in the experimental animal. The compound
in learning and memory has been reviewed by Glass- potentiates dopamine and causes partial inhibition
man (1969) and, more recently, the effect of R N A of serotonin (Hansl, 1973, 1974b). A compound with
precursors has attracted attention (Ott and Mathies, this profile might be expected to cause a favorable
1973). Compounds affecting the adrenergic and cho- shift of the balance of CNS transmitter systems,
linergic systems have been studied in detail (Krivaneck thereby improving intellectual functioning.
and McGaugh, 1969; Merlo and Izquierdo, 1971; PRL-8-53 exhibits low toxicity with an oral LDso
Robichaud et al., 1973; Deutsch and Lutzky, 1967; of 860 mg/kg in mice. Blood pressure of the normo-
Rech, 1968; Erickson, 1971). In summary, it appears tensive dog is not significantly affected by doses of
that intellectual performance and, more particularly, up to 8 mg/kg. Higher doses cause a slight drop in
retention of information can be positively affected pressure of brief duration (Hansl, 1974b). The com-
along two major pathways: (1) Facilitation of R N A pound depresses motor activity of the mouse and
synthesis during and/or shortly after the learning rat. For the mouse the EDso for a 5 0 ~ reduction is
experience will improve retention of the animal; 160 mg/kg. PRL-8-53 does not produce stimulation
(2) The action of certain analeptic stimulants and of or depression of avoidance rate in rats working on a
some 'adrenergic' CNS agonists will enhance, while continuous avoidance schedule. The compound, at
the effect of other CNS active agonists will diminish, 20 mg/kg, does not potentiate the stimulant effects
0033-3158/78/0056/0249/$1.00

PRL 8 53

Uploaded by

Copyright:

Available Formats

PRL 8 53

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

PRL 8 53

Uploaded by

Copyright:

Available Formats

Psychopharmacology 56, 249-253 (1978) Psychopharmacology

Abstract. The effect of 3-(2-benzylmethylaminoethyl) intellectual performance. It seems to be necessary for

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.