Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.11.18 (
MAP
)
7,412
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The ambulation-increasing effect of methamphetamine (
MAP
: 2 mg/kg s.c.) in mice persisted for about 3 h. Tetrabenazine (
TBZ
: 4 mg/kg s.c.), a depleter of monoamines from the cytoplasmic pool did not increase ambulation on its own. Pretreatment with
TBZ
at 1.5 h before administration of
MAP
inhibited the stimulant effect of
MAP
. In contrast, combined administration of two drugs resulted in a transient but considerable enhancement of MAPs stimulant effect. Post-
MAP
treatment with
TBZ
at 0.5-2 h hardly modified MAPs behavioral effects. In contrast, 3-6 h post-
MAP
treatment with
TBZ
induced a transient increase in activity, although the stimulant effect of
MAP
had already disappeared. The maximum increase in ambulatory stimulation was produced by 4-h post-
MAP
treatment with
TBZ
. The inhibitory effect of
TBZ
pretreatment on
MAP
-induced hyperactivity, as well as the transient hyperactivity elicited by
TBZ
when administered along with
MAP
, or 4 h after
MAP
, was dose-dependent. Preliminary studies revealed that transient hyperactivity was never produced by combination of GBR-12909 (a selective dopamine reuptake inhibitor) with
TBZ
or
MAP
with oxypertine (a selective norepinephrine releaser/depleter), but produced by combination of nialamide (a monoamine oxidase inhibitor) with
TBZ
. Inhibition of MAPs effects by
TBZ
pretreatment suggests that enhancement of dopamine release from cytoplasmic pool, and inhibition of dopamine reuptake by
MAP
, are involved in MAPs acute behavioral effects. Further, the fact that neither
TBZ
administration following GBR-12909 pretreatment, nor oxypertine treatment following
MAP
pretreatment, elicited transient hyperactivity suggests that dopamine is involved in hyperactivity elicited by post-
MAP
treatment with
TBZ
. It is also suggested that inhibition of monoamine oxidase (MAO) by
MAP
and dopamine displacement by
TBZ
may be responsible for the transient stimulation produced by 3-6 h post-
MAP
treatment with
TBZ
. It is hypothesized that the MAO inhibitory action of
MAP
persists after cessation of its acute stimulant effect, possibly up to 6 h after administration.
...
PMID:Effects of tetrabenazine on methamphetamine-induced hyperactivity in mice are dependent on order and time-course of administration. 898 3
