flunarizine and Hypothermia

Episodic spontaneous hypothermia is an infrequent disorder, the pathogenic mechanisms of which have not been completely clarified, although alterations in the serotoninergic system have been suggested. We report the history of a girl with episodes of dizziness and shivering associated with a body temperature lower than 35 degrees C since the age of 10 months. At the age of 11 years, she was admitted to a local hospital and an oral glucose tolerance test showed high total insulin levels. Hypoglycemia secondary to hyperinsulinemia was suspected, and a low-carbohydrate (simple) diet was proposed without results. Due to the recurrence of the episodes, episodic spontaneous hypothermia triggered by hyperinsulinemia was suspected, and treatment with flunarizine, a drug considered the first line in the treatment of migraine-related disorders, was started with a resulting reduction in the episodes. A new endocrinological evaluation showed decreased insulin secretion. In our patient, the success of the therapy might be due to the well-known effect of calcium antagonists in inhibiting serotonin uptake and thereby regulating serotonin levels after hyperinsulinism. This case suggests hyperinsulinemia as a potential mechanism for episodic spontaneous hypothermia, probably mediated by an interaction between insulin and the serotoninergic system.

Topics: Adolescent; Anticonvulsants; Diet, Carbohydrate-Restricted; Female; Flunarizine; Humans; Hyperinsulinism; Hypothermia; Insulin; Serotonin

Episodic spontaneous hypothermia is an infrequent disorder, with unknown pathogenic mechanisms. A systemic cause or underlying brain lesion has not been found for the disease. We report four new patients, 3-9 years old, with episodic hypothermia lower than 35 degrees C, marked facial pallor, and absent shivering. The episodes could last a few hours or four days, and recurred once a week or every 2-3 months. Two patients also demonstrated bradycardia, mild hypertension, and somnolence during the events; in one of them, profuse sweating was also a feature, and all four presented with either headache, a periodic childhood syndrome, or both (recurrent abdominal pain, cyclic vomiting, or vertigo). Three patients reported a family history of migraine. Neurologic examination, endocrine function, and imaging studies were normal. Migraine prophylactic therapy was of moderate efficacy. Spontaneous resolution was observed in one patient. The clinical characteristics of the syndrome allow for its inclusion as a childhood periodic syndrome related to migraine.

Topics: Abdominal Pain; Body Temperature; Bradycardia; Child; Child, Preschool; Consciousness Disorders; Cyproheptadine; Diagnosis, Differential; Female; Flunarizine; Genetic Predisposition to Disease; Humans; Hyperhidrosis; Hypertension; Hypothermia; Infant; Male; Migraine Disorders; Neurologic Examination; Periodicity; Reference Values; Remission, Spontaneous; Syndrome

Our earlier studies showed that dihydropyridine calcium channel antagonists have some central pharmacological effects. Flunarizine is considered to be a calcium channel antagonist; therefore this study was aimed at investigating the effect of flunarizine (given in single doses of 5, 10 and 20 mg/kg p.o.) in behavioural models in which calcium channel antagonists of the dihydropyridine type were previously studied. Flunarizine inhibited the apomorphine-induced stereotypy and yawning behaviour in rats. It decreased the hypothermia induced by a low dose of apomorphine in mice, but not that one induced by high dose of it. The quinpirole-induced hypothermia was also reduced. In the tests used for evaluation of the effect on the serotonergic system, flunarizine decreased the 5-HTP-induced head twitches and partly antagonized the fenfluramine- and quipazine-induced hyperthermias (at a high ambient temperature). In the forced swimming test flunarizine was inactive in mice and rats. The obtained results indicate that flunarizine exerts central antagonistic effects on the dopaminergic and serotonergic systems and has no antidepressant activity. Flunarizine differs from calcium channel antagonists of the dihydropyridine type, which have no dopamine-antagonistic activity and show anti-depressant-like properties.

Topics: 5-Hydroxytryptophan; Animals; Apomorphine; Body Temperature Regulation; Dopamine; Dopamine Antagonists; Drug Interactions; Ergolines; Fenfluramine; Flunarizine; Hypothermia; Male; Mice; Motor Activity; Quinpirole; Quipazine; Rats; Rats, Inbred Strains; Serotonin; Serotonin Antagonists; Species Specificity; Stereotyped Behavior; Yawning

Topics: Alveolar Process; Anesthesia, Dental; Animals; Arteries; Cattle; Fendiline; Flunarizine; Hypothermia; Hypothermia, Induced; In Vitro Techniques; Mandible; Norepinephrine; Regional Blood Flow; Temperature