Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats.
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.
Boban Blagaic
Alenka
A
Department of Pharmacology, Medical Faculty, University of Zagreb, Salata 11, POB 916, 10000 Zagreb, Croatia.
Blagaic
Vladimir
V
Mirt
Mirela
M
Jelovac
Nikola
N
Dodig
Goran
G
Rucman
Rudolf
R
Petek
Marijan
M
Turkovic
Branko
B
Anic
Tomislav
T
Dubovecak
Miroslav
M
Staresinic
Mario
M
Seiwerth
Sven
S
Sikiric
Predrag
P
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010293:Pargyline / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011506:Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020230:Serotonin Syndrome / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D014364:Tryptophan / Q000494:pharmacology / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D018687:Antidepressive Agents, Second-Generation; D008996:Monoamine Oxidase Inhibitors; D010446:Peptide Fragments; D011506:Proteins; D014364:Tryptophan; C083833:BPC 157; D010293:Pargyline