Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Terazosin, an alpha-adrenergic antagonist, was administered as a 15 mg/ml solution to rats intravenously at a rate of 2 ml/min. Under these conditions the LD50 was 277 mg/kg for males and 293 mg/kg for females. When administered daily for 1 month at dosages of 0, 10, 40 or 150 mg/kg/day, the no-toxic-effect dosage was 40 mg/kg/day. Evidence of toxicity at 150 mg/kg included hypothermia and deaths. Death resulted from acute, exaggerated pharmacologic effects leading to cardiorespiratory failure. Evidence of sympatholytic activity observed at lower dosages included hypoactivity, blepharoptosis, ptyalism and splenic congestion.
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PMID:Terazosin: intravenous safety evaluation in rats. 651 Feb 53

Terazosin, a water-soluble alpha 1 antagonist that can be administered in high doses intraventricularly was used to study the relationship between brain alpha 1 adrenoceptor neurotransmission and behavioral activation in the mouse. The antagonist was found to produce a dose-dependent, complete inhibition of motor activity and catalepsy which were reversed preferentially by coinfusion of an alpha 1 agonist (phenylephrine) compared to a D1 (SKF38393) or a D2 agonist, (quinpirole). Blockade of central beta-1 (betaxolol), alpha-2 (RX821002) or beta-2 (ICI 118551) adrenoceptors had smaller or non-significant effects. Terazosin's selectivity for alpha 1 receptors versus dopaminergic receptors was verified under the present conditions by showing that the intraventricularly administered antagonist protected striatal and cerebral cortical alpha 1 receptors but not striatal or cortical D1 receptors from in vivo alkylation by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroxyquinoline. That its effect was due to blockade of brain rather than peripheral receptors was shown by the finding that intraperitoneal doses of terazosin three to 66 times greater than the maximal intraventricular dose produced less behavioral inhibition. Intraventricular terazosin also produced hypothermia and a reduced respiratory rate suggestive of a reduced sympathetic outflow. However, external heat did not affect the inactivity, and captopril, a hypotensive agent, did not mimic it. Terazosin did not impair performance on a horizontal wire test or the ability to make co-ordinated movements in a swim test suggesting that its activity-reducing effect was not due to sedation and may have a motivational or sensory gating component. It is concluded that central alpha 1-noradrenergic neurotransmission is required for behavioral activation to environmental change in the mouse and may operate on sensorimotor and motivational processes.
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PMID:Brain alpha 1-adrenergic neurotransmission is necessary for behavioral activation to environmental change in mice. 1062 64