Disease relevance of SCH 32615

• The administration of SCH 32615 (3 mg/kg) decreased both D-1 and D-2 antagonist-induced catalepsy [1].
• Our purpose was to identify possible acute behavioral effects, neurotoxicity, or systemic toxicity of intrathecal SCH 32615 administration during 9 days in the ewe [2].

Psychiatry related information on SCH 32615

• To test this hypothesis, the effects of SCH 32615, an enkephalinase inhibitor, on DA antagonist-induced catalepsy, DA D-1 agonist-induced non-stereotyped grooming, and DA D-2 agonist-induced stereotyped behavior were studied [1].
• In the PAG and VM, SCH-32615 resulted in a dose-dependent increase in HP and TF response latencies over a dose range of 1-30 micrograms with the ED50 values (micrograms) being PAG-TF = 17; PAG-HP = 11; VM-TF = 7; VM-HP = 6 [3].

High impact information on SCH 32615

• SCH 32615, an enkephalinase inhibitor, significantly enhanced this analgesia [4].
• SCH 32615 significantly enhanced this analgesia (percentage of maximal possible effect (%MPE) at 4 h 33.7 +/- 8.7%, at 5 h 27.5 +/- 4.7%, and at 6 h 23.2 +/- 4.7%; P < 0.05 compared to all other groups), and naloxone antagonized its effect [4].
• Plasma renin activity was further suppressed with SCH 32615 pretreatment (29% compared with 20%, P < 0.001) [5].
• 3. Compared with brain natriuretic peptide (0.5 pmol min-1 kg-1) alone, SCH 32615 pretreatment increased peak plasma brain natriuretic peptide (13.4 +/- 0.78 versus 12.4 +/- 0.86 pmol/l, P < 0.05), ANP (7.5 +/- 0.96 versus 5.9 +/- 0.4 pmol/l, P < 0.01) and cGMP (4.8 +/- 1.7 versus 3.9 +/- 1.4 nmol/l, P < 0.001) [5].
• Acute toxicology of an enkephalinase inhibitor (SCH 32615) given intrathecally in the ewe [2].

Biological context of SCH 32615

• The fly endopeptidase was much less sensitive to phosphoramidon (IC50, 0.25 microM), thiorphan (IC50, 2.5 microM), SQ 28603 (IC50, 1.0 microM), SCH 39370 (IC50, 2.5 microM) and SCH 32615 (IC50, 30 microM) [6].
• SCH-32615 induced greater diuresis and natriuresis than C-ANP-(4-23) [7].

Anatomical context of SCH 32615

• Taken together, these results support the hypothesis that inhibition of the in vivo degradation of enkephalins induced by the systemic administration of SCH 32615 increases the enkephalinergic tone in the central nervous system and thereby activates the mesolimbic dopaminergic neurons [8].
• This effect appears to be mediated via opioid receptors, since it was completely prevented by naloxone (5 mg/kg s.c.). The increase in DOPAC content in the prefrontal cortex elicited by foot-shock was unaffected by pretreatment with SCH 32615 [8].
• The local effects of SCH-32615, an inhibitor of enkephalinase (EC 3.4.24.11) on the hot-plate (HP) and tail-flick (TF) responses were examined following unilateral intracerebral microinjection into the periaqueductal brain (PAG), the medial ventral medulla (VM) and bilateral microinjection into the amygdala (AM) of the rat [3].
• When administered at analgesically active doses (1-100 mg/kg s.c., 60 min before killing), SCH 32615 induced a dose-dependent increase in dopamine metabolism in the nucleus accumbens but was ineffective in the striatum and in the prefrontal cortex [8].
• SCH-32615 is a new enkephalinase inhibitor whose analgesic effects were examined following its stereotactic microinjection into the periaqueductal gray (PAG) and the ventromedial medulla (VMM) regions of the brainstem of the rat [9].

Gene context of SCH 32615

• The results indicate that SCH 32615 lacks in vivo ECE inhibitory activity [10].
• SCH 32615 failed to attenuate the pressor responses to either BET-1 or ET-1 [10].
• In vitro, the Ki for SCH 32615 to block the degradation of Met5-enkephalin by isolated enkephalinase is 19.5 +/- 0.9 nM [11].
• Airway opening pressure changes and the recovery of SP-LI and NKA-LI were significantly greater in lungs superfused with the NEP inhibitor SCH 32615 than in control lungs [12].

Analytical, diagnostic and therapeutic context of SCH 32615

• Anesthesia without surgery did not evoke subsequent analgesia, and SCH 32615 was not analgesic in the absence of antecedent surgery [4].
• One control group (n = 13) received 0.9% methylcellulose and the other 150 mg/kg SCH 32615 (n = 12) [4].
• All antinociceptive effects were antagonized by naloxone (1 mg/kg, i.p.). Twenty-four hours following the microinjection of beta-funaltrexamine (an irreversible opioid antagonist) into the PAG or the VM, the effects of SCH-32615 in the PAG were virtually abolished while in the VM, its effects were only moderately reduced [3].
• Baseline and serial daily behavioral assessments were made during 9 days of 2-mL intrathecal injection twice daily of either normal saline (SAL group) or a 20 mg/mL isotonic sterile solution of SCH 32615 (SCH group) [2].

References