Serotonin syndrome commonly follows irreversible
monoamine oxidase (
MAO)-inhibition and subsequent
serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake,
hypothermia followed by
hyperthermia). A stable gastric pentadecapeptide
BPC 157 with very safe profile (
inflammatory bowel disease clinical phase II, PL-10,
PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than
imipramine, and, given peripherally, has region specific influence on brain
5-HT synthesis (alpha-[14C]methyl-
L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic
drug. Thereby, we investigate this
peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full
serotonin syndrome in rat combining
pargyline (irreversible
MAO-inhibition; 75 mg/kg i.p.) and subsequent
L-tryptophan (5-HT precursor; 100 mg/kg i.p.;
BPC 157 as a co-treatment), or (ii, iii) using
pargyline or
L-tryptophan given separately, as a
serotonin-substrate with (ii)
pargyline (
BPC 157 as a 15-min posttreatment) or as a potential
serotonin syndrome inductor with (iii)
L-tryptophan (
BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide
BPC 157 contrasts with
serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a
serotonin substrate (counteraction of
pargyline), nor an inductor for
serotonin syndrome (no influence on
L-tryptophan challenge)). Indicatively, severe
serotonin syndrome in
pargyline +
L-tryptophan rats is considerably inhibited even by lower pentadecapeptide
BPC 157 doses regimens (particularly disturbances such as
hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in
pargyline rats (mild
hypothermia, feeble hind limbs abduction). Thereby, in severe
serotonin syndrome, gastric pentadecapeptide
BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena.