Naspm 3HCl (1-Naphthylacetyl spermine trihydrochloride), the trihydrochloride salt of Naspm, is a synthetic analog of Joro spider toxin and a calcium permeable AMPA (CP-AMPA) receptors antagonist.

Physicochemical Properties

Molecular Formula	C22H34N4O
Molecular Weight	370.53156
Exact Mass	478.203
CAS #	1049731-36-3
Related CAS #	Naspm;122306-11-0
PubChem CID	16219727
Appearance	White to off-white solid powder
LogP	6.925
Hydrogen Bond Donor Count	7
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	14
Heavy Atom Count	30
Complexity	391
Defined Atom Stereocenter Count	0
InChi Key	JNEOJAUJWOPWJS-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H34N4O.3ClH/c23-12-6-15-24-13-3-4-14-25-16-7-17-26-22(27)18-20-10-5-9-19-8-1-2-11-21(19)20;;;/h1-2,5,8-11,24-25H,3-4,6-7,12-18,23H2,(H,26,27);3*1H
Chemical Name	N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-naphthalen-1-ylacetamide;trihydrochloride
Synonyms	Naspm trihydrochloride; 1-Naphthylacetyl spermine trihydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	NASPM trihydrochloride (1-Naphthylacetyl spermine) selectively blocks inwardly rectifying, Ca²⁺-permeable AMPA-type glutamate receptors that lack or have low expression of the GluR2 subunit (IC₅₀ = 0.33 µM at −60 mV). It has no effect on outwardly rectifying, Ca²⁺-impermeable AMPA receptors containing GluR2.
ln Vitro	The Ca2+-permeable and inward rectifying AMPA receptors expressed in type II neurons are specifically inhibited by NASPM. On type I neurons' AMPA receptors, it has no impact. With an IC50 value of 0.33 µM, NASPM inhibits AMPA receptors in type II neurons at -60 mV. Applications and voltages affect how well NASPM blocks Ca2+ permeable AMPA receptors [1]. NASPM selectively suppressed kainate-induced currents in type II cultured rat hippocampal neurons, which express inwardly rectifying and Ca²⁺-permeable AMPA receptors, in a dose-dependent manner (IC₅₀ = 0.33 µM, Hill coefficient = 0.94) at a holding potential of −60 mV. The suppression reached a steady state after 15–25 ionophoretic applications of kainate, reducing the response to 11.0 ± 0.7% of control. The blockade was use-dependent and voltage-dependent; no suppression was observed at membrane potentials more positive than +40 mV. The effect was partially reversible after washing (recovery to 43.7 ± 4.5% of control). In type I neurons (expressing GluR2-containing AMPA receptors), NASPM had no effect (98.5 ± 1.1% of control). Intermediate neurons showed intermediate sensitivity. [1]
Enzyme Assay	The study utilized whole-cell patch-clamp recordings to assess the blocking effect of NASPM on AMPA receptors. Cultured rat hippocampal neurons were voltage-clamped at various holding potentials. Kainate, a non-desensitizing AMPA receptor agonist, was applied ionophoretically to the soma using high-resistance glass electrodes filled with 100 mM kainate solution. Current responses were recorded before, during, and after bath application of NASPM. The rectification index (RI) was calculated to classify neurons into type I (RI > 1.0), type II (RI < 0.25), and intermediate (0.25 ≤ RI ≤ 1.0). The voltage dependence of blockade and recovery was tested by shifting membrane potential during drug application. [1]
Cell Assay	Primary hippocampal neurons were cultured from 17–19-day-old rat embryos and used for electrophysiology 8–14 days after plating. Whole-cell recordings were performed using patch pipettes filled with an internal solution containing CsCl, EGTA, and HEPES. The external solution contained NaCl, KCl, CaCl₂, glucose, HEPES, TTX, and bicuculline. To test the effect of NASPM, the drug was bath-applied and solution exchange was controlled via peristaltic pumps. Kainate was applied ionophoretically every 3 seconds. Current responses were filtered at 1 kHz and digitized at 2 kHz. The degree of blockade was quantified as the percentage reduction in peak current amplitude compared to control. [1]
References	[1]. Blocking effect of 1-naphthyl acetyl spermine on Ca2+-permeable AMPA receptors in cultured rat hippocampal neurons. Neurosci Res. 1997 Sep;29(1):27-36.
Additional Infomation	NASPM is a synthetic analog of Joro spider toxin (JSTX-3) but is more compact and exhibits reversible blockade compared to the nearly irreversible effect of JSTX. It acts as a non-competitive antagonist of Ca²⁺-permeable AMPA receptors. The drug may serve as a useful pharmacological tool for studying the physiological and pathological roles of these receptors in the CNS, such as in synaptic plasticity, ischemia, and excitotoxic neuronal death. [1]

Solubility Data

Solubility (In Vitro)	H2O : ~50 mg/mL (~104.19 mM) DMSO : ~6.4 mg/mL (~13.34 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (208.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6988 mL	13.4942 mL	26.9884 mL
	5 mM	0.5398 mL	2.6988 mL	5.3977 mL
	10 mM	0.2699 mL	1.3494 mL	2.6988 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.