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PubMed1984

Clavines. New antibiotics with cytostatic activity.

The cytostatic potentials of ten ergolines were determined in the L5178y mouse lymphoma cell system; six of them belong to the clavines (agroclavine, 1-propyl-agroclavine, 1-propyl-festuclavine, 1-allyl-festuclavine, 6-cyano-6-nor-festuclavine and 1-hydroxymethyl-festuclavine) and four to the lysergic acid derivatives (methylergometrine, lysergic acid amide, isolysergic acid amide and lysergic acid diethylamide). It is shown that agroclavine (ED50: 3.9 microM), 1-propyl-agroclavine (3.5 microM), 1-propylfestuclavine (4.3 microM) and 1-allyl-festuclavine (4.3 microM) are potent cytostatic agents. Up to 2 X ED50 concentration the inhibitory effect was completely reversible. Incorporation studies suggested that the compounds inhibit DNA synthesis; this assumption was also supported by the findings which revealed that after incubation with these clavines, the cells showed slight 'unbalanced growth'. 6-Cyano-6-nor-festuclavine was less inhibitory (ED50 11.8 microM). 1-Hydroxymethyl-festuclavine and all lysergic acid derivatives tested were without any detectable activity.

Animals↗
PubMed1993

Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder.

Platelet serotonin (5-HT) studies were conducted with 12 hyperserotonemic and 12 normoserotonemic age-, sex-, and relationship-matched relatives of autistic probands. Each group consisted of 7 mothers, 4 fathers, and 1 sister of autistic children and adolescents. The density (Bmax) of platelet 5-HT2 receptor binding sites, labelled with [3H]-lysergic acid diethylamide (LSD), was significantly lower in 11 hyperserotonemic subjects compared to 12 normoserotonemic subjects (40.9 +/- 13.5 fmol/mg protein, 59.6 +/- 13.2; p < 0.004). The affinity (Kd) for [3H]-LSD binding did not differ. Although the density (Bmax) of [3H]-paroxetine binding did not differ between groups, there was a small difference in the affinity (Kd) for [3H]-paroxetine binding (hyperserotonemic 47.6 +/- 9.0 pM, normoserotonemic 54.8 +/- 12.1; p < 0.05). There were no significant differences in platelet 5-HT uptake, or in thrombin-stimulated 5-HT release. Basal, 5-HT-stimulated, and arginine-vasopressin (AVP)-stimulated inositol phosphate production, as well as basal, prostaglandin E1 (PGE1)-, and forskolin-stimulated cAMP production did not differ. There were significant correlations between whole blood 5-HT levels and LSD Bmax (rs = -0.63, N = 23, p < 0.002) and whole blood 5-HT levels and 5-HT uptake Vmax (rs = 0.56, N = 18, p < 0.02). However, [3H]-LSD labelled 5-HT2 binding and 5-HT uptake were not correlated with each other. Hyperserotonemia of autism may be heterogeneous with one subgroup of subjects with increased 5-HT uptake and another subgroup with decreased 5-HT2 binding.

1-Methyl-3-isobutylxanthine↗
PubMed2005

Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro.

Insomnia is the most frequently encountered sleep complaint worldwide. While many prescription drugs are used to treat insomnia, extracts of valerian (Valeriana officinalis L., Valerianaceae) are also used for the treatment of insomnia and restlessness. To determine novel mechanisms of action, radioligand binding studies were performed with valerian extracts (100% methanol, 50% methanol, dichloromethane [DCM], and petroleum ether [PE]) at the melatonin, glutamate, and GABA(A) receptors, and 8 serotonin receptor subtypes. Both DCM and PE extracts had strong binding affinity to the 5-HT(5a) receptor, but only weak binding affinity to the 5-HT(2b) and the serotonin transporter. Subsequent binding studies focused on the 5-HT(5a) receptor due to the distribution of this receptor in the suprachiasmatic nucleus of the brain, which is implicated in the sleep-wake cycle. The PE extract inhibited [(3)H]lysergic acid diethylamide (LSD) binding to the human 5-HT(5a) receptor (86% at 50 microg/ml) and the DCM extract inhibited LSD binding by 51%. Generation of an IC(50) curve for the PE extract produced a biphasic curve, thus GTP shift experiments were also performed. In the absence of GTP, the competition curve was biphasic (two affinity sites) with an IC(50) of 15.7 ng/ml for the high-affinity state and 27.7 microg/ml for the low-affinity state. The addition of GTP (100 microM) resulted in a right-hand shift of the binding curve with an IC(50) of 11.4 microg/ml. Valerenic acid, the active constituent of both extracts, had an IC(50) of 17.2 microM. These results indicate that valerian and valerenic acid are new partial agonists of the 5-HT(5a) receptor.

Animals↗
PubMed1998

Clueless: parental knowledge of risk behaviors of middle school students.

OBJECTIVES: To determine parental knowledge of risk behaviors of their middle-school-aged children and to compare that knowledge with behaviors reported by the students. DESIGN: Confidential surveys were administered to 194 poor and middle-class middle school students and their parents. INTERVENTION: None. MAIN OUTCOME MEASURE: Compare parental awareness and student admission of risk behaviors. RESULTS: Students and parents agree on the prevalence of some risk behaviors, including use of a seat belt, use of a bicycle helmet, arrest by police, use of diet pills, and attempts to lose weight through dieting and exercise. Small differences in perception, which were not statistically significant but which could be defined as trends, were found relating to the prevalence of dieting, exercising, or vomiting to lose weight. Statistically significant differences were found in the perceptions of the prevalence of the following risk behaviors: carrying a weapon to school (P<.001), LSD (lysergic acid diethylamide) or cocaine use (P=.02), suicide attempt (P<.001), sexual intercourse (P<.001), alcohol use (P<.001), tobacco use (P<.001), and marijuana use (P<.001). In many cases, parents dramatically underestimated the prevalence of these behaviors in students. CONCLUSIONS: Parents are largely ignorant of the extent to which their adolescents are involved in major risk behaviors. Educating parents in this area encourages them to support comprehensive health education curricula and other preventive programs in schools and communities.

Adolescent↗