Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports have indicated that alpha-MSH release inhibiting hormone (MIF-1) increased the behavior occurring as a result of the dihydroxyphenylalanine (DOPA) potentiation test [3,7]. This study was undertaken to see whether dopamine (DA) or norepinephrine (NE) levels likewise increased in the test animals. The DOPA potentiation test was performed as follows: 2-4 hr before behavior measurement, 40 mg/kg of the monoamine oxidase inhibitor pargyline HCl was given orally. Two hr later this was followed by the intraperitoneal (IP) injection of MIF-1 at doses of 0.1, 0.3 or 1.0 mg/kg. Behavioral measurement was begun after the IP injection of 200 mg/kg of dl-DOPA 1-2 hr after the MIF-1. The parameters included social interaction, aggressiveness, fighting, ataxia, jumping, defecation, urination and salivation. The animals were beheaded while the behavior was still increased and the striatal area removed, placed in aluminum foil, and kept at -50 degrees C until assayed. In general, especially among the younger animals, a significant correlation (p=0.05 to p=0.01) was found between the increased behavioral responses to MIF-I and the rise in DA. Because of a few exceptions to this correlation the possibility is suggested that MIF-I might also affect behavior by acting directly on the postsynaptic membrane thus bypassing any change in NE or DA which is known to increase cycli AMP in the striatum.
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PMID:Possible association of increased rat behavioral effects and increased striatal dopamine and norepinephrine levels during the DOPA-potentiation test. 1 11

alpha-MSH-related compounds may prove to be clinically useful antipyretics since the parent peptide is extremely potent in reducing fever, it is effective when given orally, and it neither stimulates corticosteroid activity nor has marked melanotropic effects in man. To determine whether or in what doses alpha-MSH might cause harmful side-effects, we injected doses greatly exceeding those required to reduce fever into a lateral cerebral ventricle of afebrile rabbits. One hundred to seven hundred and fifty micrograms alpha-MSH caused large and prolonged reductions in body temperature and the dose-response relation was bell-shaped for both magnitude and duration. These doses caused no apparent injury to the animals. One mg alpha-MSH elicited hyperthermic responses that were variable in magnitude and duration. Animals that had previously received large doses of alpha-MSH (greater than or equal to 100 micrograms) did not develop hyperthermia, even when given 2 mg, indicating an acquired tolerance to this hyperthermic action of alpha-MSH. All animals, tolerant or previously uninjected, showed symptoms with doses greater than or equal to 1 mg alpha-MSH that included: increased salivation, agitation, ataxia, respiratory distress, and death (in 30% of the animals); those that recovered from these large doses resumed outwardly healthy appearance and behavior. Although alpha-MSH is toxic when given centrally in large doses, the 5000-fold difference between antipyretic and toxic doses indicates a wide safety margin should this peptide be used clinically as an antipyretic drug.
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PMID:Effects of massive doses of alpha-MSH on thermoregulation in the rabbit. 387 78