Summary
We have studied the effects of single oral doses of amoxapine (100 mg and 200 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced double-blind crossover design.
Amitriptyline significantly reduced salivation and it significantly attenuated both miosis evoked by locally applied pilocarpine and sweat secretion evoked by locally applied carbachol. Amoxapine did not significantly alter any of these measures. Neither treatment significantly altered the pupillary light reflex (latency, amplitude, or 75% recovery time). Resting pupil diameter was significantly reduced by the higher dose of amoxapine but was not affected by the other treatments.
The higher dose of amoxapine significantly increased supine systolic blood pressure, but did not affect heart rate or diastolic blood pressure; amitriptyline had no effect on any of these cardiovascular measures.
These results confirm the antimuscarinic effects of amitriptyline in man, but provide no evidence for antimuscarinic effects of amoxapine.
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References
Arnold SE, Kahn RJ, Faldetta LL, Laing RA, McNair DM (1981) Tricyclic antidepressants and peripheral anticholinergic activity. Psychopharmacol 74: 325–328
Bakes A, Bradshaw CM, Szabadi E (1990) Attenuation of the pupillary light reflex in anxious patients. Br J Clin Pharmacol 30: 377–381
Blackwell B, Peterson GR, Kuzma RJ, Hostetler RM, Adolphe E (1980) The effect of five tricyclic antidepressants on salivary flow and mood in healthy volunteers. Comm Psychopharmacol 4: 255–261
Blackwell B, Stefoppulous A, Enders P, Kuzma R, Adolphe A (1978) Anticholinergic activity of two tricyclic antidepressants. Am J Psychiatr 135: 722–724
Bye CE, Clubley M, Henson T, Peck AW, Smith SA, Smith SE (1979) Changes in the human light reflex as a measure of the anticholinergic effects of drugs. Eur J Clin Pharmacol 15: 21–25
Calvo B, Garcia MJ, Pedraz EL, Dominguez-Gil A (1985) Pharmacokinetics of amoxapine and its active metabolites. International J Clin Pharmacol Ther Toxicol 23: 180–185
Clubley M, Bye CE, Henson T, Peck AW, Riddington C (1978) A technique for studying the effects of drugs on human sweat gland activity. Eur J Clin Pharmacol 16: 221–226
Cooper TB, Kelly RG (1979) GLC analysis of loxapine, amoxapine and their metabolites in serum and urine. J Pharm Sci 68: 216–219
Coupet J, Fisher SK, Raul CE, Lai F, Beer B (1985) Interaction of amoxapine with muscarinic cholinergic receptors: an in vitro assessment. Eur J Pharmacol 112: 231–235
El-Fakahany E, Richelson E (1983) Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Clin Pharmacol 78: 97–102
Ghose K, Dobree C, Taylor P, Turner P (1974) Interactions of amitriptyline with guanethidine and thymoxamine in the human iris. Br J Clin Pharmacol 1: 516–517
Hekimian LJ, Friedhoff AJ, Deever E (1978) A comparison of the onset of action and therapeutic efficacy of amoxapine and amitryptyline. J Clin Psychiatry 39: 633–637
Ishikawa S, Oono S, Hikita H (1977) Drugs affecting the iris muscle. In: Dikstein S (ed) Drugs and ocular tissues, Karger, Basel, pp 288–382
Jørgensen A (1975) A gas chromotographic method for the determination of amitriptyline and nortriptyline in human serum. Acta Pharmacol Toxicol 36: 79–90
Jue SG, Dawson GW, Brogden RN (1982) Amoxapine: a review of its pharmacology and efficacy in depressed states. Drugs 24: 1–23
Kopera H (1978) Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo. Br J Clin Pharmacol 5: 29S-34S
Knorring L, Mornstad H, Forsgren L, Holmgren S (1986) Acute effects of different antidepressant drugs on saliva secretion and accommodation range. Pharmacopsychiatry 19: 106–110
Lin SC, Olsen KC, Okazaki H, Richelson E (1986) Studies on muscarinic binding sites in human brain identified with (3H)pirenzepine. J Neurochem 46: 274–279
Longmore J, Berry JL, Szabadi E, Bradshaw CM (1990) A comparison of the anticholinergic effects of two formulations of disopyramide in healthy volunteers. Eur J Clin Pharmacol 39: 305–309
Longmore J, Bradshaw CM, Szabadi E (1985a) Effects of locally administered cholinoceptor antagonists on the secretory responses of human eccrine sweat glands to carbachol. Br J Clin Pharmacol 20: 1–7
Longmore J, Szabadi E, Bradshaw CM (1985b) Comparison of the effects of binodaline and amitriptyline on peripheral autonomic functions in healthy volunteers. Br J Clin Pharmacol 19: 295–300
Lowenstein O, Loewenfeld IE (1962) The pupil. In: Davson H (ed) The eye. Vol 3. Muscular mechanisms. Academic Press, New York, pp 231–267
Morley MJ, Bradshaw CM, Szabadi E (1991) Effects of clonidine and yohimbine on the pupillary light reflex and carbachol-evoked sweating in healthy volunteers. Br J Clin Pharmacol 31: 99–101
Newsome DA, Loewenfeld IE (1974) Pilocarpine re-examined: an old puzzle. Surv Ophthalmol 18: 399–424
Ogura C, Kishimoto A, Mizukawa R, Matsubayashi M, Omura F, Kunimoto N (1987) Comparative study of 9 antidepressants on several physiological parameters in healthy volunteers. Neuropsychobiol 17: 139–144
Peck RE (1959) The SHP test: an aid in the detection and measurement of depression. Arch Gen Psychiatry 1: 35–40
Richelson E, Nelson A (1984) Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther 230: 94–102
Richelson E, Pfenning M (1984) Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block morepinephrine uptake. Eur J Pharmacol 104: 277–286
Schubert DSP (1973) The effect of lithium and other anticholinergic medications on the autonomic nervous system. Curr Ther Res 15: 862–865
Szabadi E (1992) Amoxapine. In: Dollery CT (ed) Therapeutic drugs (Supplement 1) Churchill Livingstone, Edinburgh, pp 9–14
Szabadi E, Bradshaw CM (1986) Antidepressant drugs and the autonomic nervous system. In: Deakin JFW (ed) The biology of depression. Gaskell, London, pp 190–220
Szabadi E, Gaszner P, Bradshaw CM (1980) The peripheral anticholergic activity of tricyclic antidepressants: comparison of amitriptyline and desipramine in human volunteers. Br J Psychiatry 137: 433–439
Theofilopoulus N, Gray CM, Szabadi E, Bradshaw CM (1989) Comparison of the effects of fengabine, a novel antidepressant, with those of amitriptyline on psychomotor and autonomic functions in healthy volunteers. Human Psychopharmacol 4: 129–134
Theofilopoulos N, Longmore J, Kerr FA, Szabadi E, Bradshaw CM (1988) Consensual responses to mydriatic and miotic drugs. Br J Clin Pharmacol 26: 697–702
Thompson ML, Sutarman (1953) The identification and enumeration of active sweat glands in man from plastic impressions of the skin. Trans Roy Soc Trop Med Hyg 47: 412–417
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Bourne, M., Szabadi, E. & Bradshaw, C.M. A comparison of the effects of single doses of amoxapine and amitriptyline on autonomic functions in healthy volunteers. Eur J Clin Pharmacol 44, 57–62 (1993). https://doi.org/10.1007/BF00315281
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DOI: https://doi.org/10.1007/BF00315281