[Comparative study of effects of ivadal and rodedorm in insomnia in structure of borderline mental diseases] [3H]Ro 15-1788 binding sites to brain membrane of the saltwater Mugil cephalus. Zolpidem, triazolam, and diazepam decrease distress vocalizations in mouse pups: differential antagonism by flumazenil and beta-Carboline-3-carboxylate-t-butyl ester (beta-CCt). Ambien online references

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Zolpidem, a non-benzodiazepine hypnotic, was identified in the blood of 29 subjects arrested for impaired driving. Zolpidem concentrations ranged from 0.05 to 1.4 mg/L (mean 0.29 mg/L, median 0.19 mg/L). In the subjects whose cases we reviewed where zolpidem was present with other drugs and/or alcohol, symptoms reported were generally those of CNS depression. Symptoms included slow movements and reactions, slow and slurred speech, poor coordination, lack of balance, flaccid muscle tone, and horizontal and vertical gaze nystagmus. In five separate cases, where zolpidem was the only drug detected (0.08-1.40 mg/L, mean 0.65 mg/L, median 0.47 mg/L), signs of impairment included slow and slurred speech, slow reflexes, disorientation, lack of balance and coordination, and "blacking out." Although no quantitative relationship between blood concentrations and degree of driving impairment is currently possible, it is reasonable to conclude that because of its specific activity as a sleep inducer, blood concentrations consistent with therapeutic doses of zolpidem have the potential to affect driving in a negative way, and that concentrations above the normal therapeutic range would further impair a person's level of consciousness and driving ability.

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Zh Nevrol Psikhiatr Im S S Korsakova. 2001;101(2):24-6.
[Comparative study of effects of ivadal and rodedorm in insomnia in structure of borderline mental diseases]

[Article in Russian]

Tsivil'ko MA, Shinaev NN, Volkov NP.

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Comp Biochem Physiol C Toxicol Pharmacol. 2001 Mar;128(3):291-7.
[3H]Ro 15-1788 binding sites to brain membrane of the saltwater Mugil cephalus.

Betti L, Giannaccini G, Gori M, Bistocchi M, Lucacchini A.

Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie dell'Universita di Pisa, Sez. Via Bonanno 6, 56100, Pisa, Italy.

The equilibrium binding parameters of the benzodiazepine antagonist [3H]Ro 15-1788 (8-fluoro-3-carboethoxy-5,6-dihydro-5-methyl-6-oxo-4H-imidazol-[1,5-a]-1,4 benzodiazepine) were evaluated in brain membranes of the saltwater teleost fish, Mugil cephalus. To test receptor subtype specificity, displacement studies were carried out by competitive binding of [3H]Ro 15-1788 against six benzodiazepine receptor ligands, flunitrazepam [5-(2-fluoro-phenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one], alpidem [N,N-dipropyl-6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-acetamide], zolpidem [N,N-6 trimethyl-2-(4-methyl-phenyl)imidazo[1,2-a]pyridine-3-acetamide hemitartrate], and beta-CCM (methyl beta-carboline-3-carboxylate). Saturation studies showed that [3H]Ro 15-1788 bound saturatably, reversibly and with a high affinity to a single class of binding sites (Kd value of 1.18-1.5 nM and Bmax values of 124-1671 fmol/mg of protein, depending on brain regions). The highest concentration of benzodiazepine recognition sites labeled with [3H]Ro 15-1788 was present in the optic lobe and the olfactory bulb and the lowest concentration was found in the medulla oblongata, cerebellum and spinal cord. The rank order of displacement efficacy of unlabelled ligands observed suggested that central-type benzodiazepine receptors are present in one class of binding sites (Type I-like) in brain membranes of Mugil cephalus. Moreover, the uptake of 36Cl- into M. cephalus brain membrane vesicles was only marginally stimulated by concentrations of GABA that significantly enhanced the 36Cl- uptake into mammalian brain membrane vesicles. The results may indicate a different functional activity of the GABA-coupled chloride ionophore in the fish brain as compared with the mammalian brain.

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J Pharmacol Exp Ther. 2001 Apr;297(1):247-53.
Zolpidem, triazolam, and diazepam decrease distress vocalizations in mouse pups: differential antagonism by flumazenil and beta-Carboline-3-carboxylate-t-butyl ester (beta-CCt).

Rowlett JK, Tornatzky W, Cook JM, Ma C, Miczek KA.

New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Dr., Box 9102, Southborough, MA 01772-9102, USA. james_rowlett

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hms.harvard.edu

In response to stressful events, neonatal mice emit ultrasonic vocalizations (USVs), which are suppressed by BZ agonists. The present study examined the role of the benzodiazepine/alpha1 (BZ/alpha1) receptor subtype in the suppression engendered by the BZ/alpha1-preferring agonist zolpidem and the nonselective BZ agonists triazolam and diazepam. The role of BZ receptor subtypes was explored further by conducting antagonism studies using the BZ/alpha1-preferring antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt), in comparison with the nonselective BZ antagonist flumazenil. Mouse pups (CFW strain) were separated from their dam and littermates at day 7, and placed for 4 min in a test chamber with reduced ambient temperature (19 +/- 1 degrees C) for recording USVs, motor incoordination (measured as a pup rolling on its back per grid cross), and body temperature. Zolpidem, triazolam, and diazepam suppressed USVs in a dose-dependent manner, concomitant with increases in incoordination and augmentation of hypothermia. These effects of the three BZ agonists were blocked by flumazenil in a manner consistent with surmountable antagonism. The ability of zolpidem, but not triazolam or diazepam, to suppress USVs and augment hypothermia was antagonized by beta-CCt, whereas the increase in motor incoordination engendered by zolpidem, triazolam, and diazepam was not sensitive to beta-CCt administration. Collectively, these results suggest that zolpidem suppresses distress USVs in mouse pups by a mechanism distinct from that of typical BZs. Furthermore, suppression of distress USVs by zolpidem may involve BZ/alpha1 receptors and a nonanxiolytic mechanism, such as hypothermia.

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