Strychnine

Brain Res. 1991 Oct 4;561(1):77-83.

Differential blockade of bicuculline and strychnine on GABA- and glycine-induced responses in dissociated rat hippocampal pyramidal cells.[Pubmed: 1797352]

METHODS AND RESULTS:
The inhibitory effects of bicuculline (BIC) and Strychnine (STR) on GABA- and glycine-induced responses were studied in the rat dissociated hippocampal CA1 pyramidal neurons in whole-cell mode by using the conventional patch-clamp technique. Both GABA and glycine elicited inward Cl- currents in a dose-dependent manner and had almost the same maximal responses. The half-maximum dose (Ka) and Hill coefficient were 6.4 microM and 1.1 for the GABA response, and 74 microM and 1.5 for the glycine response. BIC and STR antagonized both GABA and glycine responses in a competitive manner. The blocking potency of BIC and STR on the GABA response was comparable. The half inhibition dose (IC50) was 2.7 microM for BIC and 6.7 microM for STR. STR blocked the glycine response about 3,000 x more effectively than BIC. The IC50 was 28 nM for STR and 100 microM for BIC. The BIC and STR did not have voltage-dependent blocking effects on either GABA or glycine responses.
CONCLUSIONS:
Neither GABA nor glycine showed outward rectification in their current-voltage relationships. The functional role of glycine in the rat hippocampal CA1 region is discussed.

Eur J Pharmacol. 1989 Dec 19;174(2-3):197-204.

A potent antagonist of the strychnine insensitive glycine receptor has anticonvulsant properties.[Pubmed: 2560979]

METHODS AND RESULTS:
5.7-Dinitro-quinoxaline-2.3-dione (MNQX) displaced [3H]glycine binding to cortical membranes but had no effect n [3H]3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ([3H]CPP) binding. MNQX potently antagonized N-methyl-D-aspartate (NMDA)-evoked release of [3H]GABA from cultured cortical neurones, NMDA evoked spreading depression and NMDA depolarizations in the rat neo-cortex. All of these responses were reversed by addition of glycine to the perfusion media.
CONCLUSIONS:
These results suggested that MNQX is an antagonist at the Strychnine-insensitive glycine receptor associated with the NMDA receptor/ionophore complex. Furthermore the compound was found to antagonise audiogenic seizures in DBA-2 mice indicating the potential of glycine antagonists of this type in anticonvulsant therapy.

Physiol. Behav., 1970, 5(12):1437-42.

Strychnine effects on discrimination learning in mice: Effects of dose and time of administration.[Reference: WebLink]

METHODS AND RESULTS:
Experiment 1 examined the dose response effects of posttrial injections of Strychnine sulphate (0.012–1.25 mg/kg) on learning in mice. Injections were given each day immediately after 3 massed training trials on a food reward visual discrimination task. Facilitation was found with low (0.25, 0.05, 0.10 mg/kg) and high (1.0 and 1.25 mg/kg) doses, but not with intermediate doses (0.20, 0.40, 0.80 mg/kg). Experiment 2 examined the effects of time of pre- or posttrial drug injection of two doses: 0.10 and 1.00 mg/kg. With both doses significant facilitation of learning was obtained with posttrial injection intervals of one hour or less. With 1.0 mg/kg facilitation was obtained with all pretrial injection times examined (longest interval was 1 hr). With 0.10 mg/kg significant facilitation was obtained with injections given 30 min but not 60 min pretrial.
CONCLUSIONS:
These findings are interpreted as providing further evidence that Strychnine facilitates learning by affecting posttrial neurobiological processes underlying memory storage.

Cell Mol Neurobiol. 1988 Sep;8(3):307-14.

Strychnine decreases the voltage-dependent Ca2+ current of both Aplysia and frog ganglion neurons.[Pubmed: 3265649]

1. The effects of Strychnine on the voltage-dependent Ca2+ current (ICa) were studied in physically isolated Aplysia neurons and enzymatically dissociated frog sensory neurons of the dorsal root ganglion.
METHODS AND RESULTS:
Neurons were studied under the internal perfusion and the voltage clamp condition. 2. Strychnine decreased the ICa with threshold concentrations for effect at 1 to 10 microM. The depression of ICa increased with Strychnine dose without effects on the current-voltage relation of ICa. The effects of low concentrations of Strychnine were reversible, but recovery was incomplete at higher concentrations. The potency of Strychnine was about 10 times less than that of diltiazem, an organic Ca2+ antagonist. At 100 microM the ICa of Aplysia neurons was reduced to about half of the control. This concentration of Strychnine also reduced the peak amplitude of ICa of frog sensory neurons.
CONCLUSIONS:
3. These results indicate that, in addition to its actions on transmitter responses and on Na+ and K+ currents, Strychnine has effects on ICa that have not previously been appreciated.

J Neurosci. 1983 Jan;3(1):237-42.

Strychnine blocks binaural inhibition in lateral superior olivary neurons.[Pubmed: 6822858]

The present study seeks to identify neurotransmitters mediating binaural inhibition in lateral superior olivary nucleus neurons.
METHODS AND RESULTS:
Neurons in this auditory structure receive inputs from both ears and are thought to code for localization of sound in space. Iontophoretic application of glycine during monaural stimulation was found to mimic the inhibition observed with binaural stimulation. Binaural inhibition was blocked by application of the glycine receptor antagonist, Strychnine, as were the effects of iontophoretic application of glycine. The post-Strychnine recovery time course for return of synaptically mediated binaural inhibition and recovery of the effects of iontophoretic glycine application were identical. Although the superior olivary complex (SOC) neurons displaying binaural inhibition could in some cases be inhibited by GABA, the binaural inhibition rarely was blocked by iontophoretic application of the GABA receptor antagonist, bicuculline.
CONCLUSIONS:
These findings suggest that glycine may be a neurotransmitter mediating binaural inhibition in certain SOC neurons and that the projection to the lateral superior olivary nucleus from the medial nucleus of the trapezoid body may be glycinergic.

Brain Res. 1997 Jun 6;759(1):1-8.

Neuroprotective effects of the strychnine-insensitive glycine site NMDA antagonist (R)-HA-966 in an experimental model of Parkinson's disease.[Pubmed: 9219856]

The neuroprotective effects of (R)-HA-966 and (S)-HA-966 (3-amino-1-hydroxy-2-pyrrolidinone) were examined in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced animal model of Parkinson's disease.
METHODS AND RESULTS:
Systemic pretreatment of C57 black mice with the Strychnine-insensitive glycine site antagonist, (R)-HA-966 (3-30 mg/kg, i.p.), dose-dependently attenuated MPTP-induced depletion of striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC). Pretreatment with (R)-HA-966 also significantly protected the degeneration of tyrosine hydroxylase-positive neurons in the substantia nigra of mice treated with MPTP and alleviated the acute behavioral changes caused by the neurotoxin. In contrast, the other racemic form, (S)-HA-966, neither prevented the neurochemical depletions nor the neuronal injury caused by MPTP.
CONCLUSIONS:
These results indicate that excitatory mechanisms of neurodegeneration are involved in the pathophysiology of Parkinson's disease, and that Strychnine-insensitive glycine site NMDA antagonists may serve as dopaminoprotective agents which intervene in the progressive neurodegeneration in Parkinson's disease.