Neboglamine HCl

Neboglamine is a synthetic small molecule, (4S)-4-amino-5-[(4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (PubChem CID 3074827). The earliest PubMed records describe it under the code CR 2249, from Rotta Research Laboratorium in Monza, Italy, as a compound selected from a series of glutamic acid derivatives (Garofalo et al., 1996; Lanza et al., 1997). A 2010 paper from Rottapharm, also in Monza, describes it as "a functional modulator of the glycine site on the N-methyl-D-aspartate (NMDA) receptor" (Chiusaroli et al., 2010).

The published record is small: a PubMed search for neboglamine on 13 October 2026 returns four records, and a search for its code CR 2249 adds a fifth, all rodent or brain tissue studies from 1996 to 2010.

Structure, formula and weight are from PubChem: CID 165412562 is neboglamine hydrochloride, and CID 3074827 is the free base, which is about 87.5% of the hydrochloride's mass. The PubMed abstracts do not say which salt form the studies used. Neboglamine's mirror-image form was coded CR 2361 (Pittaluga et al., 1997).

As of 13 October 2026, a PubMed search for "neboglamine" returns 4 records and a search for CR 2249, entered without quotation marks, returns the same 4 plus one more. Two are in vivo studies, one in rats and mice and one in rats (behavioral tests with microdialysis or immunohistochemistry), and three are brain slice, nerve terminal and binding studies, one of them in human cortical tissue. Each summary below names its model.

NMDA receptor assays in rat brain tissue

In rat hippocampal slices, NMDA evokes release of tritium-labeled noradrenaline, and kynurenate blocks that release at the receptor's glycine site. (S)CR 2249 at 3 to 30 µM did not significantly change glycine's potency in reversing the kynurenate block but raised the efficacy of the glycine effect in a concentration-dependent manner, and it increased [3H]MK-801 binding with positive cooperativity with glycine. The developers concluded that it "probably acts at a separate allosteric site to increase NMDA receptor functionality" (Lanza et al., 1997).

A University of Genova group found that CR 2249, but not CR 2361, potently prevented the kynurenate block in slices; in hippocampal nerve terminals (synaptosomes), glycine and D-cycloserine enhanced NMDA-evoked release while CR 2249 did not, and the authors suggested that compounds active in this test may bind sites other than the glycine site (Pittaluga et al., 1997). Models: rat hippocampal slices, synaptosomes and binding assays.

Human cortical slices

The same group repeated the assay in slices of human neocortex removed during neurosurgery. CR 2249, but not its mirror-image form CR 2361, was among the compounds that prevented the kynurenate block of NMDA-evoked noradrenaline release, alongside aniracetam, oxiracetam and D-cycloserine (Pittaluga et al., 1999). This is tissue work, not a study in people. Model: human cortical slices.

Avoidance tests and hippocampal microdialysis (rat and mouse)

The developers tested CR 2249 in step-through and step-down passive avoidance and other avoidance procedures in rats and mice, including after scopolamine or electroconvulsive shock. They reported changes in avoidance responses only when it was given 45 minutes before training, not right after training or before the retention trial, and no change in general behavior or motor activity. In freely moving rats, hippocampal microdialysis showed increased noradrenaline release and reduced efflux of its metabolite 3,4-dihydroxyphenylglycol (Garofalo et al., 1996). Models: rats and mice.

Fos immunohistochemistry and phencyclidine models (rat)

In rat forebrain, neboglamine increased Fos-like immunoreactive cells, a marker of neuronal activation, 3.2-fold in the prefrontal cortex, 4.8-fold in the nucleus accumbens and 4.5-fold in the lateral septal nucleus, with no effect in the dorsolateral striatum, where haloperidol raised them 390-fold. Its pattern closely matched that of D-serine, an endogenous agonist at the NMDA glycine site.

In frontal cortex punches exposed to phencyclidine (PCP), an NMDA antagonist, it restored NMDA-mediated neurotransmitter release. In rats it inhibited PCP-induced hyperlocomotion without changing basal locomotor activity, and given by mouth it reduced both PCP-induced hyperlocomotion and rearing, with larger effects at higher amounts (Chiusaroli et al., 2010). D-serine, clozapine and haloperidol were the comparison compounds. Models: rat brain tissue and rat behavior.

Development history

The 1996 and 1997 developer papers came from Rotta Research Laboratorium and the 2010 paper from Rottapharm, both in Monza, Italy (Garofalo et al., 1996; Chiusaroli et al., 2010); the two kynurenate test papers of 1997 and 1999 came from the University of Genova.

Neboglamine is listed in PubChem as its International Nonproprietary Name, and PubChem's drug development summary, drawn from ChEMBL, gives its maximum phase as Phase 2 without naming a study.