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Since the introduction of radioiodinated metaiodobenzylguanidine in 1980, considerable research has been performed, both in the chemical field and in medical sciences. However, despite the wide use of radioiodinated metaiodobenzylguanidine, knowledge about its pharmacology is still limited. This paper reviews the biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry of radioiodinated metaiodobenzylguanidine. Iodine-131 metaiodobenzylguanidine therapy is in general well tolerated, but its effectiveness needs improvement. Also whole-body dosimetry as part of treatment planning needs to be improved. Future prospects on these items are included in this review.

Dextran and methacrylated dextrans (dex-MA) were degraded with dextranase, and the formed degradation products were characterized by electrospray mass spectrometry. It was shown that the main degradation product was isomaltose for both dextran and dex-MA. In degraded dex-MA, the main methacrylated product was isomaltotriose. The relative contribution of oligosaccharides with a higher molecular weight (up to isomaltohexaose) and of multiply methacrylated oligosaccharides increased with the degree of substitution of dex-MA. Enzyme kinetics with a three-substrate model showed that the Michaelis−Menten constant for the monomethacrylated substrate was smaller than for the unsubstituted substrate, whereas the Michaelis−Menten constant for multiply methacrylated susbtrates was higher. This indicates a favorable interaction of one methacrylate group with a hydrophobic binding subsite in the enzyme. The maximum degradation rate, however, was substantially lower for the substituted substrates than for the native substrate. From these results, it is concluded that the enzyme hydrolyzes a glycosidic bond between a methacrylated glucopyranose residue and an unsubstituted one in the dex-MA chain. This hypothesis is further supported with electrospray mass spectrometry because of both the presence of an ion formed by fragmentation at the nonreducing end of an oligosaccharide and the absence of oligosaccharides in which the number of methacrylates equals or exceeds the number of glucopyranose residues.

The main purpose of this study was to compare the sensitivity of a driving simulator test model (TS2) with a standard on-the-road driving test, after one night treatment with lormetazepam 1 mg, oxazepam 50 mg (as a verum) and placebo. The secondary purpose was to measure the effects of the intended drugs and placebo in the same subject sample, after two treatment nights in the morning and in the afternoon, on on-the-road driving performance. Eighteen healthy male volunteers received the three treatments (2 consecutive nights each) according to a double-blind, three-way crossover design. Time of administration was set at 22.00 hours each night. An on-the-road driving test and a simulator driving test were conducted in the morning following the first night. After the second treatment night, on-the-road driving tests were performed in the morning and in the afternoon. The on-the-road driving test consisted of operating an instrumental automobile over a 100 km highway circuit at a constant speed (90 kmh) and constant steady lateral position between the right lane boundaries. Primary performance measure was the SD of lateral position (SDLP). The simulator test consisted of repeatedly performing 'curve-following' manoeuvres, which was the main tracking control task, while simultaneously reacting to secondary visual signs. Test parameters were the number of correctly executed manoeuvres (TC) and reaction time (RT). Oxazepam 50 mg seriously impaired, and lormetazepam 1 mg slightly impaired, on-the-road driving performance in the morning, both after the first and second treatment night. The drugs produced no significant effects in the afternoon test following the second night. In contrast with these results, neither oxazepam 50 mg nor lormetazepam 1 mg affected simulator tracking control after one night. No deterioration was found for reaction time. Correlational and multiple regression analyses were applied to determine relationships between SDLP, TC and RT. The major conclusion of this study was that the TS2 driving simulator test does not predict residual drug effects in the on-the-road driving test, and seems to be a less sensitive measure of sedative drug-induced impairment in contrast to the on-the-road driving test.KEY wows-Hypnotics, simulated driving, on-the-road driving. INTRODlJCTIONStudies of hypnotics have generally focused on their effects on sleep; however, it is also clear that they have effects which can extend beyond the usual sleep period. Among the risks associated with the use of hypnotics, the most prominent effect is decreased performance during the day following nocturnal administration (Hindmarch, 1980;Volkerts and O'Hanlon, 1986). This hangover or residual effect is not a side-effect, but merely an extension of the drug's primary action. It occurs because hypnotics produce sleepiness, reduce alertness, and thereby reduce performance efficiency. This poses * Author to whom correspondence should be addressed. a crucial problem for hypnotic users who must operate a motor vehicle or other dangerous m...