N-[2-hydroxy-5-[2-(methylamino)ethyl]phenyl]methanesulfonamide. A potent agonist which releases intracellular calcium by activation of alpha 1-adrenoceptors.

N-[2-Hydroxy-5-[2-(methylamino)ethyl]phenyl]methanesulfonamide (SK&F 102652) has been prepared and characterized pharmacologically. It is a potent agonist with an EC50 of 25 nM at alpha 1-adrenoceptors as determined in the isolated perfused rabbit ear artery. On the presynaptic alpha 2-adrenoceptors of the guinea pig atrium it was considerably weaker, demonstrating an EC50 for inhibition of neurotransmission of 1200 nM and thus an overall alpha 1/alpha 2 selectivity ratio of greater than or equal to 48.

Calcium utilization in the vasoconstriction to enantiomers of SK&F 89748-A.

The effects of calcium entry blockade on the vasoconstriction to the selective alpha-1 adrenoceptor agonists d- and I-SK&F 89748-A (1,2,3,4-tetrahydro-8-methoxy-[5-methylthiol] -2-naphthalenamine HCl) in pithed rats and in rat and guinea-pig isolated aortas were studied. The log-dose response curves for the increase in diastolic pressure in pithed rats to i.v.

Measurements of 45Ca2+ uptake and contractile responses after activation of postsynaptic alpha 1-adrenoceptors in the isolated canine saphenous vein: effects of calcium entry blockade.

The increase in 45Ca2+ content produced by the EC100 concentrations of a series of alpha 1-agonists in the canine saphenous vein (CSV) was determined in the presence of 10(-7) M rauwolscine and found to be correlated (r = 0.92) with the intrinsic activities of the alpha 1-agonists in CSV. The degree of inhibition of 45Ca2+ uptake by nifedipine (1 microM) was inversely correlated (r = -0.

Homogeneous clinical subgroups in children with Tourette syndrome.

The existence of two clinically homogeneous subgroups in Tourette syndrome, depending upon the presence or absence of migraine or a family history of migraine, is suggested. Patients with Tourette syndrome who have migraine (n = 18) were found to have a significantly higher prevalence of disorders of arousal--particularly sleepwalking and night terrors--as well as a higher prevalence of motion sickness than patients without migraine (n = 27). They were also significantly more likely to exhibit a co-occurrence of associated features (two or more) than the patients without migraine.

Alloantigen-activated lysis of syngenic tumor augmented by allogenic lymphocytes as cold targets.

In the past, most work in tumor immunology involved attempts to demonstrate tumor-specific transplantation antigens; however, recent in vitro work has shown that it is not necessary to sensitize to a specific tumor antigen to achieve lysis of syngenic tumor cells. Responder spleen cells from B6AF1 mice (H-2a,b) were sensitized in mixed lymphocyte cultures (MLC) to alloantigens on spleen cells from B10.D2 (H-2d) mice.

Characterization of alpha adrenoceptors on vascular smooth muscle: electrophysiological differentiation in canine saphenous vein.

The effects of selective alpha adrenoceptor agonists on resting transmembrane potential (Em) and contractile responses of vascular smooth muscle of the canine saphenous vein (CSV) were investigated using microelectrode and isometric tension recording techniques. The Em of the smooth muscle cells of the CSV was -59.5 mV +/- 0.

Postsynaptic alpha adrenoceptors on vascular smooth muscle.

A heterogeneous population of alpha adrenoceptors mediates vasoconstriction in the canine saphenous vein (CSV). Studies with isolated strips of venous smooth muscle incubated with selective alpha-adrenoceptor agonists and antagonists revealed that both alpha 1 and alpha 2 adrenoceptors exist independently in this tissue and both subtypes mediate a contractile response. Measurement of contractile responses in reduced or zero external calcium conditions indicates that stimulation of alpha 1 adrenoceptors induces contractions by influx of extracellular calcium and release of calcium from internal stores.

Tourette's syndrome and migraine.

Among 60 patients with Tourette's syndrome (TS), whose mean age was 11.9 years, migraine was prevalent in 26.6%.

Somnambulism in children with Tourette syndrome.

A total of 171 children, 57 with Tourette syndrome, 57 with learning disabilities and the rest with seizure disorders, were studied to discover the incidence of somnambulism. Of the 13 identified sleepwalkers, 10 had Tourette syndrome. It is argued that this may be due to a disturbance in serotonin metabolism.

Development of an affinity ligand for purification of alpha 2-adrenoceptors from human platelet membranes.

Human platelets contain alpha 2-adrenoceptors which are negatively coupled to the enzyme adenylate cyclase. In order to better understand the interaction of this subtype of alpha receptor with this key enzyme, we have initiated a program to isolate and characterize the alpha 2-adrenoceptor. This report describes the synthesis and biological characterization of a series of molecules that were prepared as affinity ligands for this purpose.

Children with Tourette syndrome: results of psychological tests given prior to drug treatment.

There have been several recent reports on the neuropsychological integrity of children and adults with Tourette syndrome (TS). However, the possible effects of tic-controlling medications on the test performance of subjects have not been thoroughly investigated, although drugs commonly used in the treatment of TS, such as haloperidol, have been shown to affect learning and behavior. In this study, 10 children diagnosed as having Gilles de la Tourette syndrome were individually administered a battery of psychological tests prior to starting drug treatment.

Disorders of arousal in Gilles de la Tourette's syndrome.

Disorders of arousal (somnambulism and night terrors) were significantly more common among children with Gilles de la Tourette's syndrome (n = 57) than among children with seizure disorders (n = 58) or learning disabilities (n = 53). Neurohumoral disturbances may account for the differences.

Pharmacological differentiation of postsynaptic alpha adrenoceptors in the dog saphenous vein.

The dog saphenous vein has postsynaptic subpopulations of both alpha-1 and alpha-2 adrenoceptors which are easily demonstrable using selective agonists and antagonists. Specific alpha-1 (methoxamine and SK&F 89748) or mixed alpha-1, alpha-2 (l-norepinephrine and M7) agonists as well as the specific alpha-2 agonist, BHT 920, cause concentration-related contraction of this tissue. However, maximum contractions produced by alpha-2 activation are significantly less than maximum contractions produced by alpha-1 or combined alpha-1, alpha-2 adrenoceptor activation.

Molecular mechanism for feedback regulation of C4 biosynthesis in guinea pig peritoneal macrophage.

Previous reports have shown that regulation of local extrahepatic production of complement may not reflect the regulation of plasma concentrations of the corresponding proteins and, further, that alteration of the tissue microenvironment can affect local macrophage protein synthesis. This report describes the molecular basis for control of the biosynthesis and secretion of a class III major histocompatibility complex gene product, the fourth component of complement (C4), from guinea pig macrophages by extracellular native C4 protein. The effect is specific for C4 synthesis, since production of C2 and total secreted protein was unaffected by fluid phase C4.

Alpha 1-adrenoceptor-mediated vasoconstriction in vivo to enantiomers of SK & F 89748-A.

The pressor activity of the 1-enantiomer of SK & F 89748-A, 1,2,3,4-tetrahydro-8-methoxy-5-(methylthio)-2-naphthalenamine, in pithed normotensive rats was found comparable with that of 1-phenylephrine. The d-enantiomer was half as potent. The log dose-pressor effect curves for d- and 1-SK & F 89748-A were not influenced by reserpine treatment (2 X 5 mg/kg i.

The ocular hypotensive action of SK&F 86466 in the conscious rabbit.

SK&F 86466, 6-chloro-3-methyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine, a potent and selective competitive antagonist of the alpha 2-adrenoceptor is of interest as a potential antiglaucoma agent. Following instillation into the rabbit eye, SK&F 86466 produced concentration (0.25 to 10%) dependent reductions in intraocular pressure (IOP).

Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: a 5-year longitudinal study.

Seventy children with cystic fibrosis were studied over a 5-year period to assess the relationship between serum immunoglobulin G levels and progression of cystic fibrosis lung disease. Patients were grouped according to their serum IgG values (low, normal, or high) and evaluated with serial pulmonary function testing, radiographic and immunologic studies, and clinical observation. The children with persistent hypogammaglobulinemia G showed significantly better lung function, better weight for age, fewer hospitalizations for pulmonary exacerbations, less colonization with Pseudomonas aeruginosa, and slower decline in pulmonary functions than did age-matched patients with normal or high IgG levels.

A method of calculating spinal cord transit time from potentials evoked by tibial nerve stimulation in normal subjects and in patients with spinal cord disease.

Somatosensory potentials were evoked by stimulation of the tibial nerve at the ankle and recorded over the spine and scalp in 16 normal subjects and 26 patients with known or suspected spinal cord disease, with the aim of developing a method of measuring spinal sensory conduction velocity using a tolerable number of stimuli, applied unilaterally to alert subjects. In normal subjects N21 was consistently recorded over L1 vertebra and in most subjects a complex, N27/N29/P33, was recorded over the cervical spine referred to the vertex. Constant latencies at different spinal levels and, in one subject, comparison with the latency of the ascending volley indicate that the complex was not derived from the spinal cord but from more rostral structures, and therefore only transit time, rather than velocity, could be measured.

Assessment of alpha-adrenergic receptor subtypes in isolated rat aortic segments.

The postsynaptic alpha-adrenoceptors in the isolated rat aorta have been characterized according to the sensitivity of the tissue to selective alpha 1- and alpha 2-adrenoceptor agonists and antagonists. The potency (-log EC50) order of the non-selective alpha-agonist norepinephrine and relatively selective agonists was as follows: norepinephrine (alpha 1 = alpha 2; 7.30); clonidine (alpha 2 greater than alpha 1; 7.

Effects of chemical sympathectomy by 6-hydroxydopamine on alpha-adrenoceptor-mediated pressor responses in pithed rat.

The effects of 6-hydroxydopamine (6-OHDA) treatment of neonatal and adult rats on vasopressor responses to postsynaptic alpha-adrenoceptor activation were studied in adult pithed rats. The pressor response to electrical stimulation of the thoracosympathetic outflow (T7-T9) was markedly reduced after neonatal or adult 6-OHDA treatment, indicating a functional destruction of the sympathetic input to the vasculature. Pressor response curves to injected noradrenaline (a nonselective alpha-agonist) and phenylephrine (a selective alpha 1-agonist) were shifted to the left in all 6-OHDA-treated animals.