Pentylenetetrazol

Pentylenetetrazol (188) is a drug with profound stimulatory activity on the central nervous system. As such, the agent was at one time used in shock therapy for treatment of mental disease. Although it has since been supplanted by safer methods, the agents still occupy an important role in various experimental animal models in pharmacology. Addition of hydrazine to the imino ether (186) obtained from caprolactam affords 187. Treat-... 

Research in rodents has provided evidence of solvent withdrawal. Continuous exposure to toluene for 4 days and subsequent cessation produced an increase in handling-induced convulsions for at least 2 hours after cessation (Wiley et al. 2003). A similar pattern of trichloroethane administration to rodents produced pronounced withdrawal, which was worsened by the administration of the proconvulsant drug pentylenetetrazole and attenuated by reexposure to 2,000 ppm of toluene or the administration of alcohol, pentobarbital, or midazolam (Evans and Balster 1993). 

In mice, PCP is effective in antagonizing electroshock- or pentylenetetrazol (PTZ)-induced tonic extensor convulsions and audiogenic seizures (Chen et al. 1959 Chen and Bohner 1961). In dogs,... 

This laboratory has utilized two approaches to define further the anticonvulsant properties of PCP. One approach involved a relatively simple convulsant model, pentylenetetrazol-induced convulsions. In this model, the administration of ketamine alone, or in combination with several known anticonvulsants, was tested. Ketamine, as a structural analog of PCP, shares many of the pharmacological properties associated with PCP. The second approach involved a more complex model, hippocampal-kindled seizures. 

Male Dublin-ICR white mice were administered pentylenetetrazol (dissolved in normal saline) by tail vein infusion. This slow intravenous infusion of PTZ to mice provided three consistent and easily measured endpoints for assessing anticonvulsant effects ... 

FIGURE 1. Effect of phenobarbital and ketamine on pentylenetetrazol convulsions... 

Bowyer, J.F., and Albertson, T.E. The effects of pentylenetetrazol, bicuculline and strychnine on the development of kindled seizures. Neuropharmacoloav 21 985-990, 1982. 

Potentiation or inhibition of effects of pentylenetetrazole Tail flick... 

Miller PE, Fink GB. 1973. Brain serotonin level and pentylenetetrazol seizure threshold in dieldrin and endrin treated mice. Proc West Pharmacol Soc 16 195-197. 

Baraban, S.C., Taylor, M.R., Castro, P.A., and Baier, H., Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression, Neuroscience, 131, 759-768, 2005. 

Antiseizure effects One study examined antiseizure effects of chrysin on chemically induced (pentylenetetrazol) seizures in mice (Medina et al. 1997). Peripheral (IP) administration produced inconsistent effects, but central (intracerebroventricular) injection (40 pg) had a significant anticonvulsant effect. Further, this effect was abolished by prior injection of the benzodiazepine antagonist, Ro 15-1788 (3 mg/kg IP). 

Jessup M (1996) Nicotine a gateway dmg J Am Med Womens Assoc 51 21 Jung ME, Wallis CJ, Gatch MB, Lai H (2000) Sex differences in nicotine substitution to a pentylenetetrazol discriminative stimulus during ethanol withdrawal in rats. Psychopharmacology 149 235-240... 

Merremosides B (13) and D (15) exhibited antiserotonergic activity in mice with Dgo values of 10 pg/cm and 2 pg/cm, (c/., promethazine, Dgo 2 pg/cm ) (24). Intraperitoneal administration to mice of tyrianthins VI (91), VIII (scammonin VI, 68), and IX (93) resulted in antidepressant activity. Also, the activities of tryanthi-nic acids I (94) and II (95), and the macrolactones scammonins I (63) and II (64), and tyrianthins VI (91), VIII (68), and IX (93) exhibited dose-dependent protective effects against pentylenetetrazole-induced seizures. Tyrianthin VI (91) and scammonin II (64) produced relaxant effects on spontaneous contractions in the isolated rat ileum. Finally, the administration of compounds 68 and 93-95 to mouse brain slices induced increments in the release of GABA and glutamic acid 48). 

The anticonvulsant activity of diazepam, assessed by its protection against pentylenetetrazole-induced tonic convulsions, was strongly reduced in ai-(HIOIR) mice compared to wild-type animals (Rudolph et al. 1999). Sodium phenobarbital remained fully effective as anticonvulsant in ai(HlOlR) mice. Thus, the anticonvulsant activity of benzodiazepines is partially but not fuUy mediated by ai receptors. The anticonvulsant action of zolpidem is exclusively mediated by ai receptors, since its anticonvulsant action is completely absent in ai(HlOlR) mice (Crestani et al. 2000). 

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