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The effects of bromadryl, dithiaden, chloroquine and propranolol on thrombin-stimulated rat platelet aggregation (measured turbidimetrically) and thromboxane B2 generation (detected by an RIA method) were compared with four selected physico-chemical parameters of these drugs. Platelet aggregation was inhibited in the rank order of potency: bromadryl > dithiaden > propranolol > chloroquine, which corresponded with the decrease in the net charge of the terminal methyl-(or ethyl-) groups in the side chain and with the increase of the dipole moment of drug molecules. On the other hand, the rank order of potency in which the drugs tested inhibited thromboxane B2 formation (chloroquine > dithiaden > bromadryl > propranolol) correlated well with the decline in molar refractivity of the drugs. No relationship was found between inhibitory effects of drugs and their partition coefficients. The results presented indicate that inhibition of platelet functions might consist of several types of drug-cell interactions, depend on the structure and physico-chemical properties of the drugs and cannot be estimated simply on the basis of partition coefficients.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8735816&dopt=Abstract
Brain Res. 1996 Apr 15;716(1-2):171-9.
Procaine microinjection into the lower midbrain increases brown fat and body temperatures in anesthetized rats.
Shibata M, Iriki M, Arita J, Kiyohara T, Nakashima T, Miyata S, Matsukawa T.
Yamanashi Institute of Environmental Sciences, Department of Physiology, Yamanashi Medical College, Japan.
A tonic inhibitory mechanism on heat production was studied by microinjecting procaine into various regions of the brain while recording temperature changes of the interscapular brown adipose tissue (IBAT) and rectum in urethane-anesthetized rats at room temperature of 23-25 degrees C. Procaine microinjected bilaterally (10%, 1.0 mu l/site, 1.5 mm to midline) into the midbrain and the upper- to mid-pontine area of the reticular formation increased temperatures of the IBAT and rectum. The highest temperature rise (1.02 +/- 0.11 degrees C for IBAT, 0.64 +/- 0.06 degrees C for rectum) with the shortest onset latency (1.5 +/- 0.3 min for IBAT, 4.6 +/- 1.1 min for rectum) was observed when procaine was injected into the lower midbrain (the area between 6 and 7 mm posterior to the bregma, and 6.5 to 8.5 mm deep from the cortical surface). These regions include the retrorubral field, pedunculopontine tegmental nucleus, and rubrospinal tract. Procaine-induced IBAT and rectal temperature increases were dose-dependent, and reproduced reliably from the same injection site of the same animal. Intravenous indomethacin, a prostaglandin H synthase inhibitor, did not affect procaine-induced temperature rise, and propranolol, a beta-blocker, completely blocked it. These results suggest that microinjected procaine exerts its local anesthetic effect and release a tonic inhibition resulting in a disinhibition-induced temperature increase through the enhanced central sympathetic outflow. They support the hypothesis that a bilateral tonic inhibitory mechanism on heat production exists in the lower midbrain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8738234&dopt=Abstract
Neuroendocrinology. 1996 May;63(5):415-21.
Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat.
Lacau-Mengido IM, Libertun C, Becu-Villalobos D.
Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina.
Serotonin (5-HT) receptors can be classified into at least three, possibly up to seven, classes of receptors. They comprise the 5-HT1, 5-HT2, and 5-HT3 classes, the "uncloned' 5-HT4 receptor and the recombinant receptors 5-ht5, 5-ht6 and 5-ht7. We investigated the role of different serotonin receptor types in a neuroendocrine response to the activation of the serotonergic system. Female immature rats were chosen as an experimental model as it has been shown that during the 3rd week of life, and not at later developmental stages, 5-hydroxytryptophan (5-HTP, a serotonin precursor) induces gonadotropin release in females and not in males. Besides, at this age, serotonin releases prolactin in both sexes. 5-HTP (50 mg/kg) released prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as expected. Ketanserin (5-HT2A antagonist) and methysergide (5-HT2C antagonist) blocked 5-HTP-induced prolactin release, but did not block the LH or FSH responses. Ondansetron (5-HT3 receptor antagonist) did not modify prolactin response to 5-HTP, whereas it blocked 5-HTP-induced LH and FSH release. Propranolol (5-HT1 and beta-adrenergic antagonist) blocked prolactin, LH and FSH release induced by 5-HTP. The 5-HT2C agonist 1-(3-chlorophenyl)piperazine dihydrochloride released prolactin, without modifying LH or FSH release. Methyl-quipazine and phenylbiguanide (5-HT3 agonists) increased both LH and FSH levels, without altering prolactin secretion. The present experiments indicate that serotonin acting at the 5-HT3 receptor mediates LH and FSH release in infantile female rats, whereas 5-HT2C or 2A receptor types participate in the release of prolactin at this age. 5-HT1 receptor type may be involved in the release of the three hormones, though a beta-adrenergic component of the response cannot be discarded.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8738578&dopt=Abstract
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